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Cellular and Molecular Biology

RNA modifications in cancer

British Journal of Cancer volume 129, pages 204–221 (2023)Cite this article

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Abstract

Currently, more than 170 modifications have been identified on RNA. Among these RNA modifications, various methylations account for two-thirds of total cases and exist on almost all RNAs. Roles of RNA modifications in cancer are garnering increasing interest. The research on m6A RNA methylation in cancer is in full swing at present. However, there are still many other popular RNA modifications involved in the regulation of gene expression post-transcriptionally besides m6A RNA methylation. In this review, we focus on several important RNA modifications including m1A, m5C, m7G, 2′-O-Me, Ψ and A-to-I editing in cancer, which will provide a new perspective on tumourigenesis by peeking into the complex regulatory network of epigenetic RNA modifications, transcript processing, and protein translation.

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Fig. 1
Fig. 2: Roles of m1A and m5C modifications in cancer.
Fig. 3: Role of m7G, 2′-O-Me, and Ψ modifications in cancer.
Fig. 4: Role of A-to-I editing in cancer.

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References

  1. Yang M, Mo Y, Ren D, Liu S, Zeng Z, Xiong W. Transfer RNA-derived small RNAs in tumor microenvironment. Mol Cancer. 2023;22:32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wang J, Ge J, Wang Y, Xiong F, Guo J, Jiang X, et al. EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1. Nat Commun. 2022;13:866.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Xiong F, Zhu K, Deng S, Huang H, Yang L, Gong Z, et al. AFAP1-AS1: a rising star among oncogenic long non-coding RNAs. Sci China Life Sci. 2021;64:1602–11.

    Article  CAS  PubMed  Google Scholar 

  4. Wang Y, Yan Q, Mo Y, Liu Y, Wang Y, Zhang S, et al. Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop. Mol Cancer. 2022;21:62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhao M, Wang Y, Tan F, Liu L, Hou X, Fan C, et al. Circular RNA circCCNB1 inhibits the migration and invasion of nasopharyngeal carcinoma through binding and stabilizing TJP1 mRNA. Sci China Life Sci. 2022;65:2233–47.

    Article  CAS  PubMed  Google Scholar 

  6. Ge J, Wang J, Xiong F, Jiang X, Zhu K, Wang Y, et al. Epstein-Barr virus-encoded circular RNA CircBART2.2 promotes immune escape of nasopharyngeal carcinoma by regulating PD-L1. Cancer Res. 2021;81:5074–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mo Y, Wang Y, Wang Y, Deng X, Yan Q, Fan C, et al. Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop. Mol Cancer. 2022;21:192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Boccaletto P, Stefaniak F, Ray A, Cappannini A, Mukherjee S, Purta E, et al. MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res. 2022;50:D231–d5.

    Article  CAS  PubMed  Google Scholar 

  9. Roundtree IA, Evans ME, Pan T, He C. Dynamic RNA modifications in gene expression regulation. Cell. 2017;169:1187–1200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ontiveros RJ, Stoute J, Liu KF. The chemical diversity of RNA modifications. Biochem J. 2019;476:1227–45.

    Article  CAS  PubMed  Google Scholar 

  11. Chen K, Song B, Tang Y, Wei Z, Xu Q, Su J, et al. RMDisease: a database of genetic variants that affect RNA modifications, with implications for epitranscriptome pathogenesis. Nucleic Acids Res. 2021;49:D1396–d1404.

    Article  CAS  PubMed  Google Scholar 

  12. Luo X, Li H, Liang J, Zhao Q, Xie Y, Ren J, et al. RMVar: an updated database of functional variants involved in RNA modifications. Nucleic Acids Res. 2021;49:D1405–d12.

    Article  CAS  PubMed  Google Scholar 

  13. Zhi Y, Zhang S, Zi M, Wang Y, Liu Y, Zhang M, et al. Potential applications of N(6) -methyladenosine modification in the prognosis and treatment of cancers via modulating apoptosis, autophagy, and ferroptosis. Wiley Interdiscip Rev RNA. 2022;13:e1719.

    Article  CAS  PubMed  Google Scholar 

  14. Tan F, Zhao M, Xiong F, Wang Y, Zhang S, Gong Z, et al. N6-methyladenosine-dependent signalling in cancer progression and insights into cancer therapies. J Exp Clin Cancer Res. 2021;40:146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dunn DB. The occurrence of 1-methyladenine in ribonucleic acid. Biochim Biophys Acta. 1961;46:198–200.

    Article  CAS  PubMed  Google Scholar 

  16. Li X, Xiong X, Wang K, Wang L, Shu X, Ma S, et al. Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome. Nat Chem Biol. 2016;12:311–6.

    Article  CAS  PubMed  Google Scholar 

  17. Seo KW, Kleiner RE. YTHDF2 recognition of N(1)-methyladenosine (m(1)A)-modified RNA is associated with transcript destabilization. ACS Chem Biol. 2020;15:132–9.

    Article  CAS  PubMed  Google Scholar 

  18. Zheng Q, Gan H, Yang F, Yao Y, Hao F, Hong L, et al. Cytoplasmic m(1)A reader YTHDF3 inhibits trophoblast invasion by downregulation of m(1)A-methylated IGF1R. Cell Discov. 2020;6:12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kuang W, Jin H, Yang F, Chen X, Liu J, Li T, et al. ALKBH3-dependent m(1)A demethylation of Aurora A mRNA inhibits ciliogenesis. Cell Discov. 2022;8:25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Woo HH, Chambers SK. Human ALKBH3-induced m(1)A demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells. Biochim Biophys Acta Gene Regul Mech. 2019;1862:35–46.

    Article  CAS  PubMed  Google Scholar 

  21. Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S, Peer E, Kol N, Ben-Haim MS, et al. The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. Nature. 2016;530:441–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Xiong X, Li X, Yi C. N(1)-methyladenosine methylome in messenger RNA and non-coding RNA. Curr Opin Chem Biol. 2018;45:179–86.

    Article  CAS  PubMed  Google Scholar 

  23. Liu F, Clark W, Luo G, Wang X, Fu Y, Wei J, et al. ALKBH1-mediated tRNA demethylation regulates translation. Cell. 2016;167:816–.e816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen Z, Qi M, Shen B, Luo G, Wu Y, Li J, et al. Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic Acids Res. 2019;47:2533–45.

    Article  CAS  PubMed  Google Scholar 

  25. Wang Y, Wang J, Li X, Xiong X, Wang J, Zhou Z, et al. N(1)-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nat Commun. 2021;12:6314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Richter U, Evans ME, Clark WC, Marttinen P, Shoubridge EA, Suomalainen A, et al. RNA modification landscape of the human mitochondrial tRNA(Lys) regulates protein synthesis. Nat Commun. 2018;9:3966.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Helm M, Giegé R, Florentz C. A Watson-Crick base-pair-disrupting methyl group (m1A9) is sufficient for cloverleaf folding of human mitochondrial tRNALys. Biochemistry. 1999;38:13338–46.

    Article  CAS  PubMed  Google Scholar 

  28. Bar-Yaacov D, Frumkin I, Yashiro Y, Chujo T, Ishigami Y, Chemla Y, et al. Mitochondrial 16S rRNA is methylated by tRNA methyltransferase TRMT61B in all vertebrates. PLoS Biol. 2016;14:e1002557.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sharma S, Hartmann JD, Watzinger P, Klepper A, Peifer C, Kötter P, et al. A single N(1)-methyladenosine on the large ribosomal subunit rRNA impacts locally its structure and the translation of key metabolic enzymes. Sci Rep. 2018;8:11904.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Waku T, Nakajima Y, Yokoyama W, Nomura N, Kako K, Kobayashi A, et al. NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner. J Cell Sci. 2016;129:2382–93.

    CAS  PubMed  Google Scholar 

  31. Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, et al. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 2012;40:5023–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wyatt GR. Occurrence of 5-methylcytosine in nucleic acids. Nature. 1950;166:237–8.

    Article  CAS  PubMed  Google Scholar 

  33. Dubin DT, Taylor RH. The methylation state of poly A-containing messenger RNA from cultured hamster cells. Nucleic Acids Res. 1975;2:1653–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yang X, Yang Y, Sun BF, Chen YS, Xu JW, Lai WY, et al. 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m(5)C reader. Cell Res. 2017;27:606–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Amort T, Rieder D, Wille A, Khokhlova-Cubberley D, Riml C, Trixl L, et al. Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain. Genome Biol. 2017;18:1.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Chen X, Li A, Sun BF, Yang Y, Han YN, Yuan X, et al. 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nat Cell Biol. 2019;21:978–90.

    Article  CAS  PubMed  Google Scholar 

  37. Yang Y, Wang L, Han X, Yang WL, Zhang M, Ma HL, et al. RNA 5-methylcytosine facilitates the maternal-to-zygotic transition by preventing maternal mRNA decay. Mol Cell. 2019;75:1188–.e1111.

    Article  CAS  PubMed  Google Scholar 

  38. Su J, Wu G, Ye Y, Zhang J, Zeng L, Huang X, et al. NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization. Oncogene. 2021;40:5814–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Selmi T, Hussain S, Dietmann S, Heiß M, Borland K, Flad S, et al. Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6. Nucleic Acids Res. 2021;49:1006–22.

    Article  CAS  PubMed  Google Scholar 

  40. Chen H, Yang H, Zhu X, Yadav T, Ouyang J, Truesdell SS, et al. m(5)C modification of mRNA serves a DNA damage code to promote homologous recombination. Nat Commun. 2020;11:2834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yang H, Wang Y, Xiang Y, Yadav T, Ouyang J, Phoon L, et al. FMRP promotes transcription-coupled homologous recombination via facilitating TET1-mediated m5C RNA modification demethylation. Proc Natl Acad Sci USA. 2022;119:e2116251119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nombela P, Miguel-López B, Blanco S. The role of m(6)A, m(5)C and Ψ RNA modifications in cancer: Novel therapeutic opportunities. Mol Cancer. 2021;20:18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li J, Li H, Long T, Dong H, Wang ED, Liu RJ. Archaeal NSUN6 catalyzes m5C72 modification on a wide-range of specific tRNAs. Nucleic Acids Res. 2019;47:2041–55.

    Article  CAS  PubMed  Google Scholar 

  44. Shanmugam R, Fierer J, Kaiser S, Helm M, Jurkowski TP, Jeltsch A. Cytosine methylation of tRNA-Asp by DNMT2 has a role in translation of proteins containing poly-Asp sequences. Cell Discov. 2015;1:15010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tuorto F, Herbst F, Alerasool N, Bender S, Popp O, Federico G, et al. The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J. 2015;34:2350–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sharma S, Yang J, Watzinger P, Kötter P, Entian KD. Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively. Nucleic Acids Res. 2013;41:9062–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Metodiev MD, Spåhr H, Loguercio Polosa P, Meharg C, Becker C, Altmueller J, et al. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet. 2014;10:e1004110.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Dai X, Gonzalez G, Li L, Li J, You C, Miao W, et al. YTHDF2 binds to 5-methylcytosine in RNA and modulates the maturation of ribosomal RNA. Anal Chem. 2020;92:1346–54.

    Article  CAS  PubMed  Google Scholar 

  49. Heissenberger C, Liendl L, Nagelreiter F, Gonskikh Y, Yang G, Stelzer EM, et al. Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth. Nucleic Acids Res. 2019;47:11807–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Boulias K, Greer EL. Put the pedal to the METTL1: adding internal m(7)G increases mRNA translation efficiency and augments miRNA processing. Mol Cell. 2019;74:1105–7.

    Article  CAS  PubMed  Google Scholar 

  51. Muthukrishnan S, Both GW, Furuichi Y, Shatkin AJ. 5′-Terminal 7-methylguanosine in eukaryotic mRNA is required for translation. Nature. 1975;255:33–7.

    Article  CAS  PubMed  Google Scholar 

  52. Ohira T, Suzuki T. Precursors of tRNAs are stabilized by methylguanosine cap structures. Nat Chem Biol. 2016;12:648–55.

    Article  CAS  PubMed  Google Scholar 

  53. Zhang LS, Liu C, Ma H, Dai Q, Sun HL, Luo G, et al. Transcriptome-wide mapping of internal N(7)-Methylguanosine methylome in mammalian mRNA. Mol Cell. 2019;74:1304–.e1308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Malbec L, Zhang T, Chen YS, Zhang Y, Sun BF, Shi BY, et al. Dynamic methylome of internal mRNA N(7)-methylguanosine and its regulatory role in translation. Cell Res. 2019;29:927–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Tomikawa C. 7-Methylguanosine modifications in transfer RNA (tRNA). Int J Mol Sci. 2018;19:4080.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Zhu C, Yan Q, Weng C, Hou X, Mao H, Liu D, et al. Erroneous ribosomal RNAs promote the generation of antisense ribosomal siRNA. Proc Natl Acad Sci USA. 2018;115:10082–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pandolfini L, Barbieri I, Bannister AJ, Hendrick A, Andrews B, Webster N, et al. METTL1 promotes let-7 MicroRNA processing via m7G methylation. Mol Cell. 2019;74:1278–.e1279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Dai Z, Liu H, Liao J, Huang C, Ren X, Zhu W, et al. N(7)-methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression. Mol Cell. 2021;81:3339–.e3338.

    Article  CAS  PubMed  Google Scholar 

  59. Volpon L, Culjkovic-Kraljacic B, Osborne MJ, Ramteke A, Sun Q, Niesman A, et al. Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E. Proc Natl Acad Sci USA. 2016;113:5263–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kiriakidou M, Tan GS, Lamprinaki S, De Planell-Saguer M, Nelson PT, Mourelatos Z. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell. 2007;129:1141–51.

    Article  CAS  PubMed  Google Scholar 

  61. Lin S, Liu Q, Lelyveld VS, Choe J, Szostak JW, Gregory RI. Mettl1/Wdr4-mediated m(7)G tRNA methylome is required for normal mRNA translation and embryonic stem cell self-renewal and differentiation. Mol Cell. 2018;71:244–.e245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Adamiak DA, Milecki J, Popenda M, Adamiak RW, Dauter Z, Rypniewski WR. Crystal structure of 2′-O-Me(CGCGCG)2, an RNA duplex at 1.30 A resolution. Hydration pattern of 2′-O-methylated RNA. Nucleic Acids Res. 1997;25:4599–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lacoux C, Di Marino D, Boyl PP, Zalfa F, Yan B, Ciotti MT, et al. BC1-FMRP interaction is modulated by 2′-O-methylation: RNA-binding activity of the tudor domain and translational regulation at synapses. Nucleic Acids Res. 2012;40:4086–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Abbas YM, Laudenbach BT, Martínez-Montero S, Cencic R, Habjan M, Pichlmair A, et al. Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations. Proc Natl Acad Sci USA. 2017;114:E2106–e2115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Elliott BA, Ho HT, Ranganathan SV, Vangaveti S, Ilkayeva O, Abou Assi H, et al. Modification of messenger RNA by 2′-O-methylation regulates gene expression in vivo. Nat Commun. 2019;10:3401.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Kurth HM, Mochizuki K. 2′-O-methylation stabilizes Piwi-associated small RNAs and ensures DNA elimination in Tetrahymena. Rna. 2009;15:675–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Picard-Jean F, Brand C, Tremblay-Létourneau M, Allaire A, Beaudoin MC, Boudreault S, et al. 2′-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO. PLoS ONE. 2018;13:e0193804.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Dai Q, Moshitch-Moshkovitz S, Han D, Kol N, Amariglio N, Rechavi G, et al. Nm-seq maps 2′-O-methylation sites in human mRNA with base precision. Nat Methods. 2017;14:695–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Choi J, Indrisiunaite G, DeMirci H, Ieong KW, Wang J, Petrov A, et al. 2′-O-methylation in mRNA disrupts tRNA decoding during translation elongation. Nat Struct Mol Biol. 2018;25:208–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ayadi L, Galvanin A, Pichot F, Marchand V, Motorin Y. RNA ribose methylation (2′-O-methylation): occurrence, biosynthesis and biological functions. Biochim Biophys Acta Gene Regul Mech. 2019;1862:253–69.

    Article  CAS  PubMed  Google Scholar 

  71. Decatur WA, Fournier MJ. rRNA modifications and ribosome function. Trends Biochem Sci. 2002;27:344–51.

    Article  CAS  PubMed  Google Scholar 

  72. Monaco PL, Marcel V, Diaz JJ, Catez F. 2′-O-methylation of ribosomal RNA: towards an epitranscriptomic control of translation? Biomolecules. 2018;8:106.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Newby MI, Greenbaum NL. Investigation of Overhauser effects between pseudouridine and water protons in RNA helices. Proc Natl Acad Sci USA. 2002;99:12697–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lin TY, Mehta R, Glatt S. Pseudouridines in RNAs-switching atoms means shifting paradigms. FEBS Lett. 2021;595:2310–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Malik TN, Doherty EE, Gaded VM, Hill TM, Beal PA, Emeson RB. Regulation of RNA editing by intracellular acidification. Nucleic Acids Res. 2021;49:4020–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Shen P, Yang T, Chen Q, Yuan H, Wu P, Cai B, et al. CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing. Mol Cancer. 2021;20:51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhang L, Yang CS, Varelas X, Monti S. Altered RNA editing in 3′ UTR perturbs microRNA-mediated regulation of oncogenes and tumor-suppressors. Sci Rep. 2016;6:23226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Ma CP, Liu H, Yi-Feng Chang I, Wang WC, Chen YT, Wu SM, et al. ADAR1 promotes robust hypoxia signaling via distinct regulation of multiple HIF-1α-inhibiting factors. EMBO Rep. 2019;20:e47107.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Jiang L, Hao Y, Shao C, Wu Q, Prager BC, Gimple RC, et al. ADAR1-mediated RNA editing links ganglioside catabolism to glioblastoma stem cell maintenance. J Clin Invest. 2022;132:e143397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fu L, Qin YR, Ming XY, Zuo XB, Diao YW, Zhang LY, et al. RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer. Proc Natl Acad Sci USA. 2017;114:E4631–e4640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Brümmer A, Yang Y, Chan TW, Xiao X. Structure-mediated modulation of mRNA abundance by A-to-I editing. Nat Commun. 2017;8:1255.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Nakano M, Fukami T, Gotoh S, Nakajima M. A-to-I RNA editing up-regulates human dihydrofolate reductase in breast cancer. J Biol Chem. 2017;292:4873–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ramírez-Moya J, Miliotis C, Baker AR, Gregory RI, Slack FJ, Santisteban P. An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks. Mol Cancer. 2021;20:115.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Han F, Hu M, Zhang L, Fan X, Wang J, Lou Z, et al. A-to-I RNA editing of BLCAP promotes cell proliferation by losing the inhibitory of Rb1 in colorectal cancer. Exp Cell Res. 2022;417:113209.

    Article  CAS  PubMed  Google Scholar 

  85. Song Y, An O, Ren X, Chan THM, Tay DJT, Tang SJ, et al. RNA editing mediates the functional switch of COPA in a novel mechanism of hepatocarcinogenesis. J Hepatol. 2021;74:135–47.

    Article  CAS  PubMed  Google Scholar 

  86. Chen L, Li Y, Lin CH, Chan TH, Chow RK, Song Y, et al. Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nat Med. 2013;19:209–16.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Han SW, Kim HP, Shin JY, Jeong EG, Lee WC, Kim KY, et al. RNA editing in RHOQ promotes invasion potential in colorectal cancer. J Exp Med. 2014;211:613–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Shoshan E, Mobley AK, Braeuer RR, Kamiya T, Huang L, Vasquez ME, et al. Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis. Nat Cell Biol. 2015;17:311–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Zipeto MA, Court AC, Sadarangani A, Delos Santos NP, Balaian L, Chun HJ, et al. ADAR1 activation drives leukemia stem cell self-renewal by impairing Let-7 biogenesis. Cell Stem Cell. 2016;19:177–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yang W, Chendrimada TP, Wang Q, Higuchi M, Seeburg PH, Shiekhattar R, et al. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol. 2006;13:13–21.

    Article  CAS  PubMed  Google Scholar 

  91. Wang Y, Xu X, Yu S, Jeong KJ, Zhou Z, Han L, et al. Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers. Genome Res. 2017;27:1112–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ramírez-Moya J, Baker AR, Slack FJ, Santisteban P. ADAR1-mediated RNA editing is a novel oncogenic process in thyroid cancer and regulates miR-200 activity. Oncogene. 2020;39:3738–53.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Cesarini V, Silvestris DA, Tassinari V, Tomaselli S, Alon S, Eisenberg E, et al. ADAR2/miR-589-3p axis controls glioblastoma cell migration/invasion. Nucleic Acids Res. 2018;46:2045–59.

    Article  CAS  PubMed  Google Scholar 

  94. Choudhury Y, Tay FC, Lam DH, Sandanaraj E, Tang C, Ang BT, et al. Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells. J Clin Invest. 2012;122:4059–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Paul D, Sinha AN, Ray A, Lal M, Nayak S, Sharma A, et al. A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme. Sci Rep. 2017;7:2466.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Ozanick S, Krecic A, Andersland J, Anderson JT. The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans. Rna. 2005;11:1281–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Li X, Xiong X, Zhang M, Wang K, Chen Y, Zhou J, et al. Base-resolution mapping reveals distinct m(1)A methylome in nuclear- and mitochondrial-encoded transcripts. Mol Cell. 2017;68:993–1005.e1009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Su Z, Monshaugen I, Wilson B, Wang F, Klungland A, Ougland R, et al. TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer. Nat Commun. 2022;13:2165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Chujo T, Suzuki T. Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs. Rna. 2012;18:2269–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Safra M, Sas-Chen A, Nir R, Winkler R, Nachshon A, Bar-Yaacov D, et al. The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. Nature. 2017;551:251–5.

    Article  CAS  PubMed  Google Scholar 

  101. Vilardo E, Nachbagauer C, Buzet A, Taschner A, Holzmann J, Rossmanith W. A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase-extensive moonlighting in mitochondrial tRNA biogenesis. Nucleic Acids Res. 2012;40:11583–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Oerum S, Roovers M, Rambo RP, Kopec J, Bailey HJ, Fitzpatrick F, et al. Structural insight into the human mitochondrial tRNA purine N1-methyltransferase and ribonuclease P complexes. J Biol Chem. 2018;293:12862–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kawarada L, Suzuki T, Ohira T, Hirata S, Miyauchi K, Suzuki T. ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications. Nucleic Acids Res. 2017;45:7401–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Wagner A, Hofmeister O, Rolland SG, Maiser A, Aasumets K, Schmitt S, et al. Mitochondrial Alkbh1 localizes to mtRNA granules and its knockdown induces the mitochondrial UPR in humans and C. elegans. J Cell Sci. 2019;132:jcs223891.

    Article  CAS  PubMed  Google Scholar 

  105. Rashad S, Han X, Sato K, Mishima E, Abe T, Tominaga T, et al. The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. RNA Biol. 2020;17:1092–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Aas PA, Otterlei M, Falnes PO, Vågbø CB, Skorpen F, Akbari M, et al. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003;421:859–63.

    Article  CAS  PubMed  Google Scholar 

  107. Ougland R, Zhang CM, Liiv A, Johansen RF, Seeberg E, Hou YM, et al. AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Mol Cell. 2004;16:107–16.

    Article  CAS  PubMed  Google Scholar 

  108. Wei J, Liu F, Lu Z, Fei Q, Ai Y, He PC, et al. Differential m(6)A, m(6)A(m), and m(1)A demethylation mediated by FTO in the cell nucleus and cytoplasm. Mol Cell. 2018;71:973–.e975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Dai X, Wang T, Gonzalez G, Wang Y. Identification of YTH domain-containing proteins as the readers for N1-methyladenosine in RNA. Anal Chem. 2018;90:6380–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, et al. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science. 2006;311:395–8.

    Article  CAS  PubMed  Google Scholar 

  111. Xue S, Xu H, Sun Z, Shen H, Chen S, Ouyang J, et al. Depletion of TRDMT1 affects 5-methylcytosine modification of mRNA and inhibits HEK293 cell proliferation and migration. Biochem Biophys Res Commun. 2019;520:60–66.

    Article  CAS  PubMed  Google Scholar 

  112. Brzezicha B, Schmidt M, Makalowska I, Jarmolowski A, Pienkowska J, Szweykowska-Kulinska Z. Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). Nucleic Acids Res. 2006;34:6034–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Sajini AA, Choudhury NR, Wagner RE, Bornelöv S, Selmi T, Spanos C, et al. Loss of 5-methylcytosine alters the biogenesis of vault-derived small RNAs to coordinate epidermal differentiation. Nat Commun. 2019;10:2550.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Henry BA, Kanarek JP, Kotter A, Helm M, Lee N. 5-methylcytosine modification of an Epstein-Barr virus noncoding RNA decreases its stability. Rna. 2020;26:1038–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Yuan S, Tang H, Xing J, Fan X, Cai X, Li Q, et al. Methylation by NSun2 represses the levels and function of microRNA 125b. Mol Cell Biol. 2014;34:3630–41.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Nakano S, Suzuki T, Kawarada L, Iwata H, Asano K, Suzuki T. NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met). Nat Chem Biol. 2016;12:546–51.

    Article  CAS  PubMed  Google Scholar 

  117. Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, et al. Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016;7:12039.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Yang L, Ren Z, Yan S, Zhao L, Liu J, Zhao L, et al. Nsun4 and Mettl3 mediated translational reprogramming of Sox9 promotes BMSC chondrogenic differentiation. Commun Biol. 2022;5:495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Haag S, Warda AS, Kretschmer J, Günnigmann MA, Höbartner C, Bohnsack MT. NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. Rna. 2015;21:1532–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Liu J, Huang T, Zhang Y, Zhao T, Zhao X, Chen W, et al. Sequence- and structure-selective mRNA m(5)C methylation by NSUN6 in animals. Natl Sci Rev. 2021;8:nwaa273.

    Article  CAS  PubMed  Google Scholar 

  121. Aguilo F, Li S, Balasubramaniyan N, Sancho A, Benko S, Zhang F, et al. Deposition of 5-methylcytosine on enhancer RNAs enables the coactivator function of PGC-1α. Cell Rep. 2016;14:479–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Huber SM, van Delft P, Mendil L, Bachman M, Smollett K, Werner F, et al. Formation and abundance of 5-hydroxymethylcytosine in RNA. Chembiochem. 2015;16:752–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Shen H, Ontiveros RJ, Owens MC, Liu MY, Ghanty U, Kohli RM, et al. TET-mediated 5-methylcytosine oxidation in tRNA promotes translation. J Biol Chem. 2021;296:100087.

    Article  CAS  PubMed  Google Scholar 

  124. Zhang Y, Wang C. Demethyltransferase AlkBH1 substrate diversity and relationship to human diseases. Mol Biol Rep. 2021;48:4747–56.

    Article  CAS  PubMed  Google Scholar 

  125. Eckwahl M, Xu R, Michalkiewicz J, Zhang W, Patel P, Cai Z, et al. 5-Methylcytosine RNA modifications promote retrovirus replication in an ALYREF reader protein-dependent manner. J Virol. 2020;94:e00544–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Wang JZ, Zhu W, Han J, Yang X, Zhou R, Lu HC, et al. The role of the HIF-1α/ALYREF/PKM2 axis in glycolysis and tumorigenesis of bladder cancer. Cancer Commun. 2021;41:560–75.

    Article  Google Scholar 

  127. Zheng H, Zhu M, Li W, Zhou Z, Wan X. m(5) C and m(6) A modification of long noncoding NKILA accelerates cholangiocarcinoma progression via the miR-582-3p-YAP1 axis. Liver Int. 2022;42:1144–57.

    Article  CAS  PubMed  Google Scholar 

  128. Gao W, Chen L, Lin L, Yang M, Li T, Wei H, et al. SIAH1 reverses chemoresistance in epithelial ovarian cancer via ubiquitination of YBX-1. Oncogenesis. 2022;11:13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Yan J, Liu J, Huang Z, Huang W, Lv J. FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells. Hum Cell. 2021;34:1755–64.

    Article  CAS  PubMed  Google Scholar 

  130. Mao X, Schwer B, Shuman S. Yeast mRNA cap methyltransferase is a 50-kilodalton protein encoded by an essential gene. Mol Cell Biol. 1995;15:4167–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Trotman JB, Giltmier AJ, Mukherjee C, Schoenberg DR. RNA guanine-7 methyltransferase catalyzes the methylation of cytoplasmically recapped RNAs. Nucleic Acids Res. 2017;45:10726–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Gonatopoulos-Pournatzis T, Dunn S, Bounds R, Cowling VH. RAM/Fam103a1 is required for mRNA cap methylation. Mol Cell. 2011;44:585–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Bueren-Calabuig JA, G Bage M, Cowling VH, Pisliakov AV. Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations. Nucleic Acids Res. 2019;47:8675–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Alexandrov A, Martzen MR, Phizicky EM. Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. Rna. 2002;8:1253–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Ma J, Han H, Huang Y, Yang C, Zheng S, Cai T, et al. METTL1/WDR4-mediated m(7)G tRNA modifications and m(7)G codon usage promote mRNA translation and lung cancer progression. Mol Ther. 2021;29:3422–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Chen Z, Zhu W, Zhu S, Sun K, Liao J, Liu H, et al. METTL1 promotes hepatocarcinogenesis via m(7) G tRNA modification-dependent translation control. Clin Transl Med. 2021;11:e661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Chen J, Li K, Chen J, Wang X, Ling R, Cheng M, et al. Aberrant translation regulated by METTL1/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression. Cancer Commun. 2022;42:223–44.

    Article  Google Scholar 

  138. Chen B, Jiang W, Huang Y, Zhang J, Yu P, Wu L, et al. N(7)-methylguanosine tRNA modification promotes tumorigenesis and chemoresistance through WNT/β-catenin pathway in nasopharyngeal carcinoma. Oncogene. 2022;41:2239–53.

    Article  CAS  PubMed  Google Scholar 

  139. Ying X, Liu B, Yuan Z, Huang Y, Chen C, Jiang X, et al. METTL1-m(7) G-EGFR/EFEMP1 axis promotes the bladder cancer development. Clin Transl Med. 2021;11:e675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Zhao Y, Kong L, Pei Z, Li F, Li C, Sun X, et al. m7G methyltransferase METTL1 promotes post-ischemic angiogenesis via promoting VEGFA mRNA translation. Front Cell Dev Biol. 2021;9:642080.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Létoquart J, Huvelle E, Wacheul L, Bourgeois G, Zorbas C, Graille M, et al. Structural and functional studies of Bud23-Trm112 reveal 18S rRNA N7-G1575 methylation occurs on late 40S precursor ribosomes. Proc Natl Acad Sci USA. 2014;111:E5518–5526.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Haag S, Kretschmer J, Bohnsack MT. WBSCR22/Merm1 is required for late nuclear pre-ribosomal RNA processing and mediates N7-methylation of G1639 in human 18S rRNA. Rna. 2015;21:180–7.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Joshi B, Lee K, Maeder DL, Jagus R. Phylogenetic analysis of eIF4E-family members. BMC Evolut Biol. 2005;5:48.

    Article  Google Scholar 

  144. Carroll M, Borden KL. The oncogene eIF4E: using biochemical insights to target cancer. J Interferon Cytokine Res. 2013;33:227–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Culjkovic B, Topisirovic I, Borden KL. Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E. Cell Cycle. 2007;6:65–69.

    Article  CAS  PubMed  Google Scholar 

  146. Zhang X, Chapat C, Wang P, Choi JH, Li Q, Luo J, et al. microRNA-induced translational control of antiviral immunity by the cap-binding protein 4EHP. Mol Cell. 2021;81:1187–.e1185.

    Article  CAS  PubMed  Google Scholar 

  147. Christie M, Igreja C. eIF4E-homologous protein (4EHP): a multifarious cap-binding protein. FEBS J. 2023;290;266–85.

  148. Jeong SJ, Park S, Nguyen LT, Hwang J, Lee EY, Giong HK, et al. A threonyl-tRNA synthetase-mediated translation initiation machinery. Nat Commun. 2019;10:1357.

    Article  PubMed  PubMed Central  Google Scholar 

  149. von Stechow L, Typas D, Carreras Puigvert J, Oort L, Siddappa R, Pines A, et al. The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. Mol Cell Biol. 2015;35:1254–68.

    Article  Google Scholar 

  150. Volpon L, Osborne MJ, Culjkovic-Kraljacic B, Borden KL. eIF4E3, a new actor in mRNA metabolism and tumor suppression. Cell Cycle. 2013;12:1159–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Weiss B, Allen GE, Kloehn J, Abid K, Jaquier-Gubler P, Curran JA. eIF4E3 forms an active eIF4F complex during stresses (eIF4FS) targeting mTOR and re-programs the translatome. Nucleic Acids Res. 2021;49:5159–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Li H, Dong H, Xu B, Xiong QP, Li CT, Yang WQ, et al. A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription. EMBOJ. 2022;41:e108544.

    Article  CAS  Google Scholar 

  153. Guy MP, Phizicky EM. Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes. Rna. 2015;21:61–74.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Nagayoshi Y, Chujo T, Hirata S, Nakatsuka H, Chen CW, Takakura M, et al. Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability. Sci Adv. 2021;7:eabf3072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Li J, Wang YN, Xu BS, Liu YP, Zhou M, Long T, et al. Intellectual disability-associated gene ftsj1 is responsible for 2′-O-methylation of specific tRNAs. EMBO Rep. 2020;21:e50095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Freund I, Buhl DK, Boutin S, Kotter A, Pichot F, Marchand V, et al. 2′-O-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recognition of whole organisms. Rna. 2019;25:869–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Lee KW, Bogenhagen DF. Assignment of 2′-O-methyltransferases to modification sites on the mammalian mitochondrial large subunit 16 S ribosomal RNA (rRNA). J Biol Chem. 2014;289:24936–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Simabuco FM, Morello LG, Aragão AZ, Paes Leme AF, Zanchin NI. Proteomic characterization of the human FTSJ3 preribosomal complexes. J Proteome Res. 2012;11:3112–26.

    Article  CAS  PubMed  Google Scholar 

  159. Ringeard M, Marchand V, Decroly E, Motorin Y, Bennasser Y. FTSJ3 is an RNA 2′-O-methyltransferase recruited by HIV to avoid innate immune sensing. Nature. 2019;565:500–4.

    Article  CAS  PubMed  Google Scholar 

  160. Liang H, Jiao Z, Rong W, Qu S, Liao Z, Sun X, et al. 3′-Terminal 2′-O-methylation of lung cancer miR-21-5p enhances its stability and association with Argonaute 2. Nucleic Acids Res. 2020;48:7027–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Lim SL, Qu ZP, Kortschak RD, Lawrence DM, Geoghegan J, Hempfling AL, et al. HENMT1 and piRNA stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse. PLoS Genet. 2015;11:e1005620.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Bélanger F, Stepinski J, Darzynkiewicz E, Pelletier J. Characterization of hMTr1, a human Cap1 2′-O-ribose methyltransferase. J Biol Chem. 2010;285:33037–44.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Werner M, Purta E, Kaminska KH, Cymerman IA, Campbell DA, Mittra B, et al. 2′-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family. Nucleic Acids Res. 2011;39:4756–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Rintala-Dempsey AC, Kothe U. Eukaryotic stand-alone pseudouridine synthases—RNA modifying enzymes and emerging regulators of gene expression? RNA Biol. 2017;14:1185–96.

    Article  PubMed  PubMed Central  Google Scholar 

  165. Borchardt EK, Martinez NM, Gilbert WV. Regulation and function of RNA pseudouridylation in human cells. Annu Rev Genet. 2020;54:309–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Carlile TM, Martinez NM, Schaening C, Su A, Bell TA, Zinshteyn B, et al. mRNA structure determines modification by pseudouridine synthase 1. Nat Chem Biol. 2019;15:966–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Martinez NM, Su A, Burns MC, Nussbacher JK, Schaening C, Sathe S, et al. Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing. Mol Cell. 2022;82:645–.e649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Shaheen R, Han L, Faqeih E, Ewida N, Alobeid E, Phizicky EM, et al. A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition. Hum Genet. 2016;135:707–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Safra M, Nir R, Farouq D, Vainberg Slutskin I, Schwartz S. TRUB1 is the predominant pseudouridine synthase acting on mammalian mRNA via a predictable and conserved code. Genome Res. 2017;27:393–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Mukhopadhyay S, Deogharia M, Gupta R. Mammalian nuclear TRUB1, mitochondrial TRUB2, and cytoplasmic PUS10 produce conserved pseudouridine 55 in different sets of tRNA. Rna. 2021;27:66–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Antonicka H, Choquet K, Lin ZY, Gingras AC, Kleinman CL, Shoubridge EA. A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Rep. 2017;18:28–38.

    Article  CAS  PubMed  Google Scholar 

  172. Guzzi N, Cieśla M, Ngoc PCT, Lang S, Arora S, Dimitriou M, et al. Pseudouridylation of tRNA-derived fragments steers translational control in stem cells. Cell. 2018;173:1204–.e1226.

    Article  CAS  PubMed  Google Scholar 

  173. Zhang DY, Ming GL, Song H. PUS7: a targetable epitranscriptomic regulator of glioblastoma growth. Trends Pharmacol Sci. 2021;42:976–8.

    Article  CAS  PubMed  Google Scholar 

  174. Zaganelli S, Rebelo-Guiomar P, Maundrell K, Rozanska A, Pierredon S, Powell CA, et al. The Pseudouridine synthase RPUSD4 is an essential component of mitochondrial RNA granules. J Biol Chem. 2017;292:4519–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Song J, Zhuang Y, Zhu C, Meng H, Lu B, Xie B, et al. Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation. Nat Chem Biol. 2020;16:160–9.

    Article  CAS  PubMed  Google Scholar 

  176. Kamalampeta R, Kothe U. Archaeal proteins Nop10 and Gar1 increase the catalytic activity of Cbf5 in pseudouridylating tRNA. Sci Rep. 2012;2:663.

    Article  PubMed  PubMed Central  Google Scholar 

  177. Duan J, Li L, Lu J, Wang W, Ye K. Structural mechanism of substrate RNA recruitment in H/ACA RNA-guided pseudouridine synthase. Mol Cell. 2009;34:427–39.

    Article  CAS  PubMed  Google Scholar 

  178. Caton EA, Kelly EK, Kamalampeta R, Kothe U. Efficient RNA pseudouridylation by eukaryotic H/ACA ribonucleoproteins requires high affinity binding and correct positioning of guide RNA. Nucleic Acids Res. 2018;46:905–16.

    Article  CAS  PubMed  Google Scholar 

  179. Meier UT. The many facets of H/ACA ribonucleoproteins. Chromosoma 2005;114:1–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Levi O, Arava YS. Pseudouridine-mediated translation control of mRNA by methionine aminoacyl tRNA synthetase. Nucleic Acids Res. 2021;49:432–43.

    Article  CAS  PubMed  Google Scholar 

  181. Wu G, Adachi H, Ge J, Stephenson D, Query CC, Yu YT. Pseudouridines in U2 snRNA stimulate the ATPase activity of Prp5 during spliceosome assembly. EMBOJ. 2016;35:654–67.

    Article  CAS  Google Scholar 

  182. Schaub M, Keller W. RNA editing by adenosine deaminases generates RNA and protein diversity. Biochimie. 2002;84:791–803.

    Article  CAS  PubMed  Google Scholar 

  183. Eisenberg E, Levanon EY. A-to-I RNA editing—immune protector and transcriptome diversifier. Nat Rev Genet. 2018;19:473–90.

    Article  CAS  PubMed  Google Scholar 

  184. Keegan LP, Leroy A, Sproul D, OConnell MA. Adenosine deaminases acting on RNA (ADARs): RNA-editing enzymes. Genome Biol. 2004;5:209.

    Article  PubMed  PubMed Central  Google Scholar 

  185. Melcher T, Maas S, Herb A, Sprengel R, Higuchi M, Seeburg PH. RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J Biol Chem. 1996;271:31795–8.

    Article  CAS  PubMed  Google Scholar 

  186. Oakes E, Anderson A, Cohen-Gadol A, Hundley HA. Adenosine deaminase that acts on RNA 3 (ADAR3) binding to glutamate receptor subunit B pre-mRNA inhibits RNA editing in glioblastoma. J Biol Chem. 2017;292:4326–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Torres AG, Piñeyro D, Filonava L, Stracker TH, Batlle E, Ribas de Pouplana L. A-to-I editing on tRNAs: biochemical, biological and evolutionary implications. FEBS Lett. 2014;588:4279–86.

    Article  CAS  PubMed  Google Scholar 

  188. Zheng Q, Yu X, Zhang Q, He Y, Guo W. Genetic characteristics and prognostic implications of m1A regulators in pancreatic cancer. Biosci Rep. 2021;41:BSR20210337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Gao Y, Wang H, Li H, Ye X, Xia Y, Yuan S, et al. Integrated analyses of m(1)A regulator-mediated modification patterns in tumor microenvironment-infiltrating immune cells in colon cancer. Oncoimmunology. 2021;10:1936758.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Liu J, Chen C, Wang Y, Qian C, Wei J, Xing Y, et al. Comprehensive of N1-methyladenosine modifications patterns and immunological characteristics in ovarian cancer. Front Immunol. 2021;12:746647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Gao L, Chen R, Sugimoto M, Mizuta M, Kishimoto Y, Omori K. The impact of m1A methylation modification patterns on tumor immune microenvironment and prognosis in oral squamous cell carcinoma. Int J Mol Sci. 2021;22:19.

    Article  Google Scholar 

  192. Esteve-Puig R, Climent F, Piñeyro D, Domingo-Domènech E, Davalos V, Encuentra M, et al. Epigenetic loss of m1A RNA demethylase ALKBH3 in Hodgkin lymphoma targets collagen, conferring poor clinical outcome. Blood. 2021;137:994–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Zhao Y, Zhao Q, Kaboli PJ, Shen J, Li M, Wu X, et al. m1A regulated genes modulate PI3K/AKT/mTOR and ErbB pathways in gastrointestinal cancer. Transl Oncol. 2019;12:1323–33.

    Article  PubMed  PubMed Central  Google Scholar 

  194. Shi L, Yang XM, Tang DD, Liu G, Yuan P, Yang Y, et al. Expression and significance of m1A transmethylase, hTrm6p/hTrm61p and its related gene hTrm6/hTrm61 in bladder urothelial carcinoma. Am J Cancer Res. 2015;5:2169–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Zhang Q, Zheng Q, Yu X, He Y, Guo W. Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues. J Transl Med. 2020;18:245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Huang W, Qi CB, Lv SW, Xie M, Feng YQ, Huang WH, et al. Determination of DNA and RNA methylation in circulating tumor cells by mass spectrometry. Anal Chem. 2016;88:1378–84.

    Article  CAS  PubMed  Google Scholar 

  197. Wang L, Zhang J, Su Y, Maimaitiyiming Y, Yang S, Shen Z, et al. Distinct roles of m(5)C RNA methyltransferase NSUN2 in major gynecologic cancers. Front Oncol. 2022;12:786266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Chen L, Ding J, Wang B, Chen X, Ying X, Yu Z, et al. RNA methyltransferase NSUN2 promotes hypopharyngeal squamous cell carcinoma proliferation and migration by enhancing TEAD1 expression in an m(5)C-dependent manner. Exp Cell Res. 2021;404:112664.

    Article  CAS  PubMed  Google Scholar 

  199. Hu Y, Chen C, Tong X, Chen S, Hu X, Pan B, et al. NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation. Cell Death Dis. 2021;12:842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Liu J, Ren Z, Yang L, Zhu L, Li Y, Bie C, et al. The NSUN5-FTH1/FTL pathway mediates ferroptosis in bone marrow-derived mesenchymal stem cells. Cell Death Discov. 2022;8:99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Mei L, Shen C, Miao R, Wang JZ, Cao MD, Zhang YS, et al. RNA methyltransferase NSUN2 promotes gastric cancer cell proliferation by repressing p57(Kip2) by an m(5)C-dependent manner. Cell Death Dis. 2020;11:270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Sun Z, Xue S, Zhang M, Xu H, Hu X, Chen S, et al. Aberrant NSUN2-mediated m(5)C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma. Oncogene. 2020;39:6906–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Piserà A, Campo A, Campo S. Structure and functions of the translation initiation factor eIF4E and its role in cancer development and treatment. J Genet Genomics = Yi Chuan Xue Bao. 2018;45:13–24.

    Article  PubMed  Google Scholar 

  204. Cowling VH. Enhanced mRNA cap methylation increases cyclin D1 expression and promotes cell transformation. Oncogene 2010;29:930–6.

    Article  CAS  PubMed  Google Scholar 

  205. Posternak V, Ung MH, Cheng C, Cole MD. MYC mediates mRNA cap methylation of canonical Wnt/β-catenin signaling transcripts by recruiting CDK7 and RNA methyltransferase. Mol Cancer Res. 2017;15:213–24.

    Article  CAS  PubMed  Google Scholar 

  206. Han H, Yang C, Ma J, Zhang S, Zheng S, Ling R, et al. N(7)-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis. Nat Commun. 2022;13:1478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Orellana EA, Liu Q, Yankova E, Pirouz M, De Braekeleer E, Zhang W, et al. METTL1-mediated m(7)G modification of Arg-TCT tRNA drives oncogenic transformation. Mol Cell. 2021;81:3323–.e3314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Liu Y, Yang C, Zhao Y, Chi Q, Wang Z, Sun B. Overexpressed methyltransferase-like 1 (METTL1) increased chemosensitivity of colon cancer cells to cisplatin by regulating miR-149-3p/S100A4/p53 axis. Aging. 2019;11:12328–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Jansson MD, Häfner SJ, Altinel K, Tehler D, Krogh N, Jakobsen E, et al. Regulation of translation by site-specific ribosomal RNA methylation. Nat Struct Mol Biol. 2021;28:889–99.

    Article  CAS  PubMed  Google Scholar 

  210. Zhou F, Liu Y, Rohde C, Pauli C, Gerloff D, Köhn M, et al. AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Nat Cell Biol. 2017;19:844–55.

    Article  CAS  PubMed  Google Scholar 

  211. Pauli C, Liu Y, Rohde C, Cui C, Fijalkowska D, Gerloff D, et al. Site-specific methylation of 18S ribosomal RNA by SNORD42A is required for acute myeloid leukemia cell proliferation. Blood. 2020;135:2059–70.

    Article  PubMed  Google Scholar 

  212. Metge BJ, Kammerud SC, Pruitt HC, Shevde LA, Samant RS. Hypoxia re-programs 2′-O-Me modifications on ribosomal RNA. iScience. 2021;24:102010.

    Article  CAS  PubMed  Google Scholar 

  213. Yi Y, Li Y, Meng Q, Li Q, Li F, Lu B, et al. A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation. Nat Cell Biol. 2021;23:341–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Guerrieri AN, Zacchini F, Onofrillo C, Di Viggiano S, Penzo M, Ansuini A, et al. DKC1 overexpression induces a more aggressive cellular behavior and increases intrinsic ribosomal activity in immortalized mammary gland cells. Cancers. 2020;12:3512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Bellodi C, Krasnykh O, Haynes N, Theodoropoulou M, Peng G, Montanaro L, et al. Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. Cancer Res. 2010;70:6026–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Cui Q, Yin K, Zhang X, Ye P, Chen X, Chao J, et al. Targeting PUS7 suppresses tRNA pseudouridylation and glioblastoma tumorigenesis. Nat Cancer. 2021;2:932–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Kan G, Wang Z, Sheng C, Chen G, Yao C, Mao Y, et al. Dual inhibition of DKC1 and MEK1/2 synergistically restrains the growth of colorectal cancer cells. Adv Sci. 2021;8:2004344.

    Article  CAS  Google Scholar 

  218. Peng X, Xu X, Wang Y, Hawke DH, Yu S, Han L, et al. A-to-I RNA editing contributes to proteomic diversity in cancer. Cancer Cell. 2018;33:817–.e817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Han L, Diao L, Yu S, Xu X, Li J, Zhang R, et al. The genomic landscape and clinical relevance of A-to-I RNA editing in human cancers. Cancer Cell. 2015;28:515–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Ruan H, Li Q, Liu Y, Liu Y, Lussier C, Diao L, et al. GPEdit: the genetic and pharmacogenomic landscape of A-to-I RNA editing in cancers. Nucleic Acids Res. 2022;50:D1231–d1237.

    Article  CAS  PubMed  Google Scholar 

  221. Galeano F, Rossetti C, Tomaselli S, Cifaldi L, Lezzerini M, Pezzullo M, et al. ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis. Oncogene. 2013;32:998–1009.

    Article  CAS  PubMed  Google Scholar 

  222. Chen YB, Liao XY, Zhang JB, Wang F, Qin HD, Zhang L, et al. ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma. Int J Oncol. 2017;50:622–30.

    Article  CAS  PubMed  Google Scholar 

  223. Gumireddy K, Li A, Kossenkov AV, Sakurai M, Yan J, Li Y, et al. The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis. Nat Commun. 2016;7:10715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Peng L, Zhang H, Su Y, Shen Q, Du C, Xie H, et al. Lipopolysaccharide enhances ADAR2 which drives Hirschsprung′s disease by impairing miR-142-3p biogenesis. J Cell Mol Med. 2018;22:4045–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  226. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12:31–46.

    Article  CAS  PubMed  Google Scholar 

  227. Jiang X, Deng X, Wang J, Mo Y, Shi L, Wei F, et al. BPIFB1 inhibits vasculogenic mimicry via downregulation of GLUT1-mediated H3K27 acetylation in nasopharyngeal carcinoma. Oncogene. 2022;41:233–45.

    Article  PubMed  Google Scholar 

  228. Mo Y, Wang Y, Zhang S, Xiong F, Yan Q, Jiang X, et al. Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2. Mol Cancer. 2021;20:112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Zhong Y, Yang L, Xiong F, He Y, Tang Y, Shi L, et al. Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc. Signal Transduct Target Ther. 2021;6:240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Fan C, Zhang S, Gong Z, Li X, Xiang B, Deng H, et al. Emerging role of metabolic reprogramming in tumor immune evasion and immunotherapy. Sci China Life Sci. 2021;64:534–47.

    Article  PubMed  Google Scholar 

  231. Tang L, Xiong W, Zhang L, Wang D, Wang Y, Wu Y, et al. circSETD3 regulates MAPRE1 through miR-615-5p and miR-1538 sponges to promote migration and invasion in nasopharyngeal carcinoma. Oncogene. 2021;40:307–21.

    Article  CAS  PubMed  Google Scholar 

  232. Fan C, Qu H, Xiong F, Tang Y, Tang T, Zhang L, et al. CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling. Cancer Lett. 2021;496:41–56.

    Article  CAS  PubMed  Google Scholar 

  233. Wang M, Dai M, Wang D, Tang T, Xiong F, Xiang B, et al. The long noncoding RNA AATBC promotes breast cancer migration and invasion by interacting with YBX1 and activating the YAP1/Hippo signaling pathway. Cancer Lett. 2021;512:60–72.

    Article  CAS  PubMed  Google Scholar 

  234. Wei X, Chen Y, Jiang X, Peng M, Liu Y, Mo Y, et al. Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments. Mol Cancer. 2021;20:7.

    Article  PubMed  PubMed Central  Google Scholar 

  235. Dai DL, Li X, Wang L, Xie C, Jin Y, Zeng MS, et al. Identification of an N6-methyladenosine-mediated positive feedback loop that promotes Epstein-Barr virus infection. J Biol Chem. 2021;296:100547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Chi Y, Liang Z, Guo Y, Chen D, Lu L, Lin J, et al. WBSCR22 confers cell survival and predicts poor prognosis in glioma. Brain Res Bull. 2020;161:1–12.

    Article  CAS  PubMed  Google Scholar 

  237. Khan AA, Huang H, Zhao Y, Li H, Pan R, Wang S, et al. WBSCR22 and TRMT112 synergistically suppress cell proliferation, invasion and tumorigenesis in pancreatic cancer via transcriptional regulation of ISG15. Int J Oncol. 2022;60:24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Jack K, Bellodi C, Landry DM, Niederer RO, Meskauskas A, Musalgaonkar S, et al. rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells. Mol Cell. 2011;44:660–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Nachmani D, Bothmer AH, Grisendi S, Mele A, Bothmer D, Lee JD, et al. Germline NPM1 mutations lead to altered rRNA 2′-O-methylation and cause dyskeratosis congenita. Nat Genet. 2019;51:1518–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Wang B, Niu L, Wang Z, Zhao Z. RNA m1A methyltransferase TRMT6 predicts poorer prognosis and promotes malignant behavior in glioma. Front Mol Biosci. 2021;8:692130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Wang Q, Zhang Q, Huang Y, Zhang J. m(1)A regulator TRMT10C predicts poorer survival and contributes to malignant behavior in gynecological cancers. DNA Cell Biol. 2020;39:1767–78.

    Article  CAS  PubMed  Google Scholar 

  242. Jiang Z, Li S, Han MJ, Hu GM, Cheng P. High expression of NSUN5 promotes cell proliferation via cell cycle regulation in colorectal cancer. Am J Transl Res. 2020;12:3858–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  243. Liu Y, Zhang Y, Chi Q, Wang Z, Sun B. Methyltransferase-like 1 (METTL1) served as a tumor suppressor in colon cancer by activating 7-methyguanosine (m7G) regulated let-7e miRNA/HMGA2 axis. Life Sci. 2020;249:117480.

    Article  CAS  PubMed  Google Scholar 

  244. Tian QH, Zhang MF, Zeng JS, Luo RG, Wen Y, Chen J, et al. METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via PTEN. J Mol Med. 2019;97:1535–45.

    Article  CAS  PubMed  Google Scholar 

  245. Wang C, Wang W, Han X, Du L, Li A, Huang G. Methyltransferase-like 1 regulates lung adenocarcinoma A549 cell proliferation and autophagy via the AKT/mTORC1 signaling pathway. Oncol Lett. 2021;21:330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Xia P, Zhang H, Xu K, Jiang X, Gao M, Wang G, et al. MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma. Cell Death Dis. 2021;12:691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Yan D, Tu L, Yuan H, Fang J, Cheng L, Zheng X, et al. WBSCR22 confers oxaliplatin resistance in human colorectal cancer. Sci Rep. 2017;7:15443.

    Article  PubMed  PubMed Central  Google Scholar 

  248. Zhao H, Su W, Sun Y, Wu Z. WBSCR22 competes with long non-coding RNA Linc00346 for miR-509-5p binding site to regulate cancer stem cell phenotypes of colorectal cancer. Biochem Genet. 2020;58:384–98.

    Article  CAS  PubMed  Google Scholar 

  249. Zhao H, Su W, Kang Q, Xing Z, Lin X, Wu Z. Natural killer cells inhibit oxaliplatin-resistant colorectal cancer by repressing WBSCR22 via upregulating microRNA-146b-5p. Am J Cancer Res. 2018;8:824–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  250. Hou P, Shi P, Jiang T, Yin H, Chu S, Shi M, et al. DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer. Br J Cancer. 2020;122:668–79.

    Article  CAS  PubMed  Google Scholar 

  251. Kan G, Wang Z, Sheng C, Yao C, Mao Y, Chen S. Inhibition of DKC1 induces telomere-related senescence and apoptosis in lung adenocarcinoma. J Transl Med. 2021;19:161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Zhang M, Pan Y, Jiang R, Hou P, Shan H, Chen F, et al. DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway. Oncol Rep. 2018;40:968–78.

    CAS  PubMed  Google Scholar 

  253. O’Brien R, Tran SL, Maritz MF, Liu B, Kong CF, Purgato S, et al. MYC-driven neuroblastomas are addicted to a telomerase-independent function of dyskerin. Cancer Res. 2016;76:3604–17.

    Article  PubMed  Google Scholar 

  254. Song D, Guo M, Xu S, Song X, Bai B, Li Z, et al. HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance. J Exp Clin Cancer Res: CR. 2021;40:170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Du J, Gong A, Zhao X, Wang G. Pseudouridylate synthase 7 promotes cell proliferation and invasion in colon cancer through activating PI3K/AKT/mTOR signaling pathway. Dig Dis Sci. 2022;67:1260–70.

    Article  CAS  PubMed  Google Scholar 

  256. He Q, Yang L, Gao K, Ding P, Chen Q, Xiong J, et al. FTSJ1 regulates tRNA 2′-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression. Cell Death Dis. 2020;11:348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Liu B, Li J, Zheng M, Ge J, Li J, Yu P. MiR-542-3p exerts tumor suppressive functions in non-small cell lung cancer cells by upregulating FTSJ2. Life Sci. 2017;188:87–95.

    Article  CAS  PubMed  Google Scholar 

  258. Manning M, Jiang Y, Wang R, Liu L, Rode S, Bonahoom M, et al. Pan-cancer analysis of RNA methyltransferases identifies FTSJ3 as a potential regulator of breast cancer progression. RNA Biol. 2020;17:474–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Wu H, Qin W, Lu S, Wang X, Zhang J, Sun T, et al. Long noncoding RNA ZFAS1 promoting small nucleolar RNA-mediated 2′-O-methylation via NOP58 recruitment in colorectal cancer. Mol Cancer. 2020;19:95.

    Article  PubMed  PubMed Central  Google Scholar 

  260. Velazquez-Torres G, Shoshan E, Ivan C, Huang L, Fuentes-Mattei E, Paret H, et al. A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression. Nat Commun. 2018;9:461.

    Article  PubMed  PubMed Central  Google Scholar 

  261. Kung CP, Cottrell KA, Ryu S, Bramel ER, Kladney RD, Bao EA, et al. Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer. Oncogene. 2021;40:189–202.

    Article  CAS  PubMed  Google Scholar 

  262. Liu X, Fu Y, Huang J, Wu M, Zhang Z, Xu R, et al. ADAR1 promotes the epithelial-to-mesenchymal transition and stem-like cell phenotype of oral cancer by facilitating oncogenic microRNA maturation. J Exp Clin Cancer Res. 2019;38:315.

    Article  PubMed  PubMed Central  Google Scholar 

  263. Zhang Y, Wang K, Zhao Z, Sun S, Zhang K, Huang R, et al. ADAR3 expression is an independent prognostic factor in lower-grade diffuse gliomas and positively correlated with the editing level of GRIA2(Q607R). Cancer Cell Int. 2018;18:196.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The figures are created with Biorender.com.

Funding

This study was supported by grants from the National Natural Science Foundation of China (U21A20382, U20A20367 and 82072374), the Overseas Expertise Introduction Project for Discipline Innovation (BP1221008), the Natural Science Foundation of Hunan Province (2021JJ30897).

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Authors and Affiliations

  1. NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410078, Changsha, Hunan, China

    Qiling Tang, Lvyuan Li, Pan Wu, Xiangchan Hou, Jiawei Ouyang, Chunmei Fan, Qianjin Liao, Hui Wang, Bo Xiang, Guiyuan Li, Zhaoyang Zeng & Wei Xiong

  2. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, 410078, Changsha, Hunan, China

    Qiling Tang, Lvyuan Li, Yumin Wang, Pan Wu, Xiangchan Hou, Jiawei Ouyang, Chunmei Fan, Zheng Li, Fuyan Wang, Can Guo, Ming Zhou, Bo Xiang, Guiyuan Li, Zhaoyang Zeng & Wei Xiong

  3. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China

    Yumin Wang & Weihong Jiang

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Contributions

TQL, LLY, WYM, WP, HXC, OYJW, FCM, LZ, WFY, GC, ZM, LQJ and WH collected the relevant literature and drafted the manuscript. XB, JWH, LGY, ZZY and XW participated in the inception and revision of the manuscript. All authors read and approved the final manuscript.

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Tang, Q., Li, L., Wang, Y. et al. RNA modifications in cancer. Br J Cancer 129, 204–221 (2023). https://doi.org/10.1038/s41416-023-02275-1

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