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Are snoRNAs and snoRNA host genes new players in cancer?

Abstract

Small nucleolar RNAs (snoRNAs) have long been considered important but unglamorous elements in the production of the protein synthesis machinery of the cell. Recently, however, several independent lines of evidence have indicated that these non-coding RNAs might have crucial roles in controlling cell behaviour, and snoRNA dysfunction could consequently contribute to oncogenesis in previously unsuspected ways.

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Figure 1: Principal features of the two classes of snoRNA and their pathway of synthesis in mammals.
Figure 2: Potential functions of the GAS5 host gene.
Figure 3: A microRNA and snoRNA-mediated p53 positive-feedback loop.

References

  1. Lestrade, L. & Weber, M. J. snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res. 34, D158–D162 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. Kiss-Laszlo, Z., Henry, Y., Bachellerie, J., Caizergues-Ferrer, M. & Kiss, T. Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell 85, 1077–1088 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. Tollervey, D. & Kiss, T. Function and synthesis of small nucleolar RNAs. Curr. Opin. Cell Biol. 9, 337–342 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Weinstein L. B., Steitz J. A. Guided tours: from precursor snoRNA to functional snoRNP. Curr. Opin. Cell Biol. 11, 378–384 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Mattick, J. & Makunin, I. Non-coding RNA. Hum. Mol. Genet. 15, R17–R29 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Decatur, W. & Fournier, M. rRNA modifications and ribosome function. Trends Biochem. Sci. 27, 344–351 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Tycowski K. T., Shu M., Kukoyi A., Steitz J. A. A conserved WD40 protein binds the cajal body localization signal of scaRNP particles. Mol. Cell 34, 47–57 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tycowski, K. T., Shu, M. D. & Steitz, J. A. A mammalian gene with introns instead of exons generating stable RNA products. Nature 379, 464–466 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Smith, C. M. & Steitz, J. A. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5 ′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol. Cell. Biol. 18, 6897–6909 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dieci, G., Preti, M. & Montanini, B. Eukaryotic snoRNAs: a paradigm for gene expression flexibility. Genomics 94, 83–88 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Hoeppner, M. P., White, S., Jeffares, D. C. & Poole, A. M. Evolutionarily stable association of intronic snornas and micrornas with their host genes. Genome Biol. Evol. 1, 420–428 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kino, T., Hurt, D. E., Ichijo, T., Nader, N. & Chrousos, G. P. Noncoding RNA Gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci. Signal. 3, ra8 (2010).

    PubMed  PubMed Central  Google Scholar 

  13. Askarian-Amiri, M. E. et al. SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA 17, 878–891 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Williams, G. T. et al. Isolation of genes controlling apoptosis through their effects on cell survival. Gene Ther. Mol. Biol. 10B, 255–261 (2006).

    Google Scholar 

  15. Mourtada-Maarabouni, M., Hedge, V. L., Kirkham, L., Farzaneh, F. & Williams, G. T. Growth arrest in human T-cells is controlled by the non-coding RNA growth-arrest-specific transcript 5 (GAS5) J. Cell Sci. 121, 939–946 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Mourtada-Maarabouni, M., Pickard, M. R., Hedge, V. L., Farzaneh, F. & Williams, G. T. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene 28, 195–208 (2009).

    Article  CAS  PubMed  Google Scholar 

  17. Dong, X. et al. Implication of snoRNA U50 in human breast cancer. J. Genet. Genomics 36, 447–454 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dong, X. et al. SnoRNA U50 is a candidate tumor-suppressor gene at 6q14.3 with a mutation associated with clinically significant prostate cancer. Hum. Mol. Genet. 17, 1031–1042 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Gee, H. E. et al. The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis. Br. J. Cancer 104, 1168–1177 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liao, J. et al. Small nucleolar RNA signatures as biomarkers for non-small-cell lung cancer. Mol. Cancer 9, 198 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Martens-Uzunova, E. S. et al. Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer. Oncogene 18 Jul 2011 (doi:10.1038/onc.2011.304).

  22. Scott, M. S. & Ono, M. From snoRNA to miRNA: dual function regulatory non-coding RNAs. Biochimie 93, 1987–1992 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kishore, S. & Stamm, S. The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311, 230–232 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Sahoo, T. et al. Prader-Willi phenotype caused by paternal deficiency for the HBII-85C/D box small nucleolar RNA cluster. Nature Genet. 40, 719–721 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Kishore, S. et al. The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing. Hum. Mol. Genet. 19, 1153–1164 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tanaka, R. et al. Intronic U50 small-nucleolar-RNA (snoRNA) host gene of no protein-coding potential is mapped at the chromosome breakpoint t(3;6)(q27;q15) of human B-cell lymphoma. Genes Cells 5, 277–287 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Mei, Y.-P. et al. Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis. Oncogene 10 Oct 2011 (doi:10.1038/onc.2011.449).

  28. Testa, J. et al. Advances in the analysis of chromosome alterations in human lung carcinomas. Cancer Genet. Cytogenet. 95, 20–32 (1997).

    Article  CAS  PubMed  Google Scholar 

  29. Michel, C. I. et al. Small Nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic stress. Cell Metab. 14, 33–44 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Montanaro, L. Dyskerin and cancer: more than telomerase. The defect in mRNA translation helps in explaining how a proliferative defect leads to cancer. J. Pathol. 222, 345–349 (2010).

    Article  CAS  PubMed  Google Scholar 

  31. Batista, L. F. Z. et al. Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474, 399–402 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hirose, T. & Steitz, J. Position within the host intron is critical for efficient processing of box C/D snoRNAs in mammalian cells. Proc. Natl Acad. Sci. USA 98, 12914–12919 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Meyuhas, O. Synthesis of the translational apparatus is regulated at the translational level. Eur. J. Biochem. 267, 6321–6330 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Yamashita, A. et al. SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay. Genes Dev. 23, 1091–1105 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schneider, C., King, R. M. & Philipson, L. Genes specifically expressed at growth arrest of mammalian-cells. Cell 54, 787–793 (1988).

    Article  CAS  PubMed  Google Scholar 

  36. Mourtada-Maarabouni, M., Hasan, A. M., Farzaneh, F. & Williams, G. T. Inhibition of human T-cell proliferation by mammalian target of rapamycin (mTOR) antagonists requires noncoding RNA growth-arrest-specific transcript 5 (GAS5). Mol. Pharmacol. 78, 19–28 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Williams, G. T., Mourtada-Maarabouni, M. & Farzaneh, F. A critical role for non-coding RNA GAS5 in growth arrest and rapamycin inhibition in human T-lymphocytes. Biochem. Soc. Trans. 39, 482–486 (2011).

    Article  CAS  PubMed  Google Scholar 

  38. Meyuhas, O. & Dreazen, A. Ribosomal protein S6 kinase: from TOP mRNAs to cell size. Prog. Mol. Biol. Transl. Sci. 90, 109–153 (2009).

    Article  CAS  PubMed  Google Scholar 

  39. Loreni, F., Iadevaia, V., Tino, E., Caldarola, S. & Amaldi, F. RACK1 mRNA translation is regulated via a rapamycin-sensitive pathway and coordinated with ribosomal protein synthesis. FEBS Lett. 579, 5517–5520 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Chitpatima, S., Makrides, S., Bandyopadhyay, R. & Brawerman, G. Nucleotide-sequence of a major messenger-RNA for a 21 kilodalton polypeptide that is under translational control in mouse-tumor cells. Nucleic Acids Res. 16, 2350–2350 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Michiels, L., Vanderrauwelaert, E., Vanhasselt, F., Kas, K. & Merregaert, J. Fau cDNA encodes a ubiquitin-like-S30 fusion protein and is expressed as an antisense sequence in the finkel-biskis-reilly murine sarcoma-virus. Oncogene 8, 2537–2546 (1993).

    CAS  PubMed  Google Scholar 

  42. Mourtada-Maarabouni, M., Kirkham, L., Farzaneh, F. & Williams, G. T. Functional expression cloning reveals a central role for the receptor for activated protein kinase C 1 (RACK1) in T cell apoptosis. J. Leukoc. Biol. 78, 503–514 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Mourtada-Maarabouni, M., Kirkham, L., Farzaneh, F. & Williams, G. T. Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression. Oncogene 23, 9419–9426 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Telerman, A. & Amson, R. The molecular programme of tumour reversion: the steps beyond malignant transformation. Nature Rev. Cancer 9, 206–215 (2009).

    Article  CAS  Google Scholar 

  45. Dean, J. L. E., Sully, G., Clark, A. R. & Saklatvala, J. The involvement of AU-rich element-binding proteins in p38 mitogen-activated protein kinase pathway-mediated mRNA stabilisation. Cell. Signal. 16, 1113–1121 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Kakegawa, T. et al. Identification of AUF1 as a rapamycin-responsive binding protein to the 5′-terminal oligopyrimidine element of mRNAs. Arch. Biochem. Biophys. 465, 274–281 (2007).

    Article  CAS  PubMed  Google Scholar 

  47. Schultze, F. C., Petrova, D. T., Oellerich, M., Armstrong, V. W. & Asif, A. R. Differential proteome and phosphoproteome signatures in human T-lymphoblast cells induced by sirolimus. Cell Prolif. 43, 396–404 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shchors, K. et al. Cell death inhibiting RNA (CDIR) derived from a 3 '-untranslated region binds AUF1 and heat shock protein 27. J. Biol. Chem. 277, 47061–47072 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Ender, C. et al. A human snoRNA with microRNA-like functions. Mol. Cell 32, 519–528 (2008).

    Article  CAS  PubMed  Google Scholar 

  50. Scott, M. S., Avolio, F., Ono, M., Lamond, A. I. & Barton, G. J. Human miRNA precursors with box H/ACA snoRNA features. PLoS Comput. Biol. 5, e1000507 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Ono, M. et al. Identification of human miRNA precursors that resemble box C/D snoRNAs. Nucleic Acids Res. 39, 3879–3891 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Esquela-Kerscher, A. & Slack, F. Oncomirs - microRNAs with a role in cancer. Nature Rev. Cancer 6, 259–269 (2006).

    Article  CAS  Google Scholar 

  53. Brameier, M., Herwig, A., Reinhardt, R., Walter, L. & Gruber, J. Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs. Nucleic Acids Res. 39, 675–686 (2011).

    Article  CAS  PubMed  Google Scholar 

  54. Xiao, J., Lin, H., Luo, X., Luo, X. & Wang, Z. miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress. EMBO J. 30, 524–532 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Montanaro, L., Trere, D. & Derenzini, M. Nucleolus, ribosomes, and cancer. Am. J. Pathol. 173, 301–310 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Shiue, C.-N., Berkson, R. G. & Wright, A. P. H. c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells. Oncogene 28, 1833–1842 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Novina, C. D. & Chabner, B. A. RNA-directed therapy: the next step in the miRNA revolution. Oncologist 13, 1–3 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Liu, X., Song, W., Sun, T., Zhang, P. & Wang, J. Targeted delivery of antisense inhibitor of miRNA for antiangiogenesis therapy using cRGD-functionalized nanoparticles. Mol. Pharm. 8, 250–259 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Doniger, T., Michaeli, S. & Unger, R. Families of H/ACA ncRNA molecules in trypanosomatids. RNA Biol. 6, 370–374 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. Liang, X., Liu, Q., Liu, Q., King, T. H. & Fournier, M. J. Strong dependence between functional domains in a dual-function snoRNA infers coupling of rRNA processing and modification events. Nucleic Acids Res. 38, 3376–3387 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Leukaemia and Lymphoma Research, Breast Cancer Campaign and the National Cancer Research Institute UK Prostate Cancer Collaborative for financial support and apologize to those authors whose work has not been cited because of space constraints. The authors also acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. Work in F.F.'s laboratory is also supported by Rosetrees Trust, Elimination of Leukaemia Fund and the Experimental Cancer Medicine Centre at King's College London.

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Williams, G., Farzaneh, F. Are snoRNAs and snoRNA host genes new players in cancer?. Nat Rev Cancer 12, 84–88 (2012). https://doi.org/10.1038/nrc3195

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