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Transcriptome-wide dynamics of RNA pseudouridylation

Nature Reviews Molecular Cell Biology volume 16, pages 581–585 (2015)Cite this article

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Abstract

Pseudouridylation is the most abundant internal post-transcriptional modification of stable RNAs, with fundamental roles in the biogenesis and function of spliceosomal small nuclear RNAs (snRNAs) and ribosomal RNAs (rRNAs). Recently, the first transcriptome-wide maps of RNA pseudouridylation were published, greatly expanding the catalogue of known pseudouridylated RNAs. These data have further implicated RNA pseudouridylation in the cellular stress response and, moreover, have established that mRNAs are also targets of pseudouridine synthases, potentially representing a novel mechanism for expanding the complexity of the cellular proteome.

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Figure 1: Constitutive and inducible pseudouridylation.
Figure 2: Possible roles of pseudouridines in gene regulation.
Figure 3: The occurrence and function of pseudouridines in various eukaryotic RNAs.

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References

  1. Cohn, W. E. Some results of the applications of ion-exchange chromatography to nucleic acid chemistry. J. Cell. Physiol. Suppl. 38, 21–40 (1951).

    Article  CAS  Google Scholar 

  2. Cohn, W. E. 5-ribosyl uracil, a carbon-carbon ribofuranosyl nucleoside in ribonucleic acids. Biochim. Biophys. Acta 32, 569–571 (1959).

    Article  CAS  Google Scholar 

  3. Cohn, W. E. Pseudouridine, a carbon-carbon linked ribonucleoside in ribonucleic acids: isolation, structure, and chemical characteristics. J. Biol. Chem. 235, 1488–1498 (1960).

    CAS  PubMed  Google Scholar 

  4. Arnez, J. G. & Steitz, T. A. Crystal structure of unmodified tRNAGln complexed with glutaminyl-tRNA synthetase and ATP suggests a possible role for pseudo-uridines in stabilization of RNA structure. Biochemistry 33, 7560–7567 (1994).

    Article  CAS  Google Scholar 

  5. Charette, M. & Gray, M. W. Pseudouridine in RNA: what, where, how, and why. IUBMB Life 49, 341–351 (2000).

    Article  CAS  Google Scholar 

  6. Karijolich, J., Kantartzis, A. & Yu, Y.-T. RNA modifications: a mechanism that modulates gene expression. Methods Mol. Biol. 629, 1–19 (2010).

    Article  CAS  Google Scholar 

  7. Spenkuch, F., Motorin, Y. & Helm, M. Pseudouridine: still mysterious, but never a fake (uridine)! RNA Biol. 11, 1540–1554 (2014).

    Article  Google Scholar 

  8. Ganot, P., Bortolin, M. L. & Kiss, T. Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. Cell 89, 799–809 (1997).

    Article  CAS  Google Scholar 

  9. Ni, J., Tien, A. L. & Fournier, M. J. Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell 89, 565–573 (1997).

    Article  CAS  Google Scholar 

  10. Wu, G., Xiao, M., Yang, C. & Yu, Y.-T. U2 snRNA is inducibly pseudouridylated at novel sites by Pus7p and snR81 RNP. EMBO J. 30, 79–89 (2011).

    Article  Google Scholar 

  11. Meier, U. T. Pseudouridylation goes regulatory. EMBO J. 30, 3–4 (2011).

    Article  CAS  Google Scholar 

  12. Basak, A. & Query, C. C. A pseudouridine residue in the spliceosome core is part of the filamentous growth program in yeast. Cell Rep. 8, 966–973 (2014).

    Article  CAS  Google Scholar 

  13. Carlile, T. M. et al. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515, 143–146 (2014).

    Article  CAS  Google Scholar 

  14. Lovejoy, A. F., Riordan, D. P. & Brown, P. O. Transcriptome-wide mapping of pseudouridines: pseudouridine synthases modify specific mRNAs in S. cerevisiae. PLoS ONE 9, e110799 (2014).

    Article  Google Scholar 

  15. Schwartz, S. et al. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159, 148–162 (2014).

    Article  CAS  Google Scholar 

  16. Darzacq, X. et al. Cajal body-specific small nuclear RNAs: a novel class of 2′-O-methylation and pseudouridylation guide RNAs. EMBO J. 21, 2746–2756 (2002).

    Article  CAS  Google Scholar 

  17. Deryusheva, S. & Gall, J. G. Small Cajal body-specific RNAs of Drosophila function in the absence of Cajal bodies. Mol. Biol. Cell 20, 5250–5259 (2009).

    Article  CAS  Google Scholar 

  18. Zhao, X., Li, Z.-H., Terns, R. M., Terns, M. P. & Yu, Y.-T. An H/ACA guide RNA directs U2 pseudouridylation at two different sites in the branchpoint recognition region in Xenopus oocytes. RNA 8, 1515–1525 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Huttenhofer, A. et al. RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse. EMBO J. 20, 2943–2953 (2001).

    Article  CAS  Google Scholar 

  20. Vitali, P. et al. Identification of 13 novel human modification guide RNAs. Nucleic Acids Res. 31, 6543–6551 (2003).

    Article  CAS  Google Scholar 

  21. Kiss, A. M., Jady, B. E., Bertrand, E. & Kiss, T. Human box H/ACA pseudouridylation guide RNA machinery. Mol. Cell. Biol. 24, 5797–5807 (2004).

    Article  CAS  Google Scholar 

  22. Chen, C., Zhao, X., Kierzek, R. & Yu, Y.-T. A flexible RNA backbone within the polypyrimidine tract is required for U2AF65 binding and pre-mRNA splicing in vivo. Mol. Cell. Biol. 30, 4108–4119 (2010).

    Article  CAS  Google Scholar 

  23. Karijolich, J. & Yu, Y.-T. Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 474, 395–398 (2011).

    Article  CAS  Google Scholar 

  24. Fernandez, I. S. et al. Unusual base pairing during the decoding of a stop codon by the ribosome. Nature 500, 107–110 (2013).

    Article  CAS  Google Scholar 

  25. Parisien, M., Yi, C. & Pan, T. Rationalization and prediction of selective decoding of pseudouridine-modified nonsense and sense codons. RNA 18, 355–367 (2012).

    Article  CAS  Google Scholar 

  26. Kariko, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008).

    Article  CAS  Google Scholar 

  27. Kishore, S. et al. Insights into snoRNA biogenesis and processing from PAR-CLIP of snoRNA core proteins and small RNA sequencing. Genome Biol. 14, R45 (2013).

    Article  Google Scholar 

  28. Ofengand, J. & Bakin, A. Mapping to nucleotide resolution of pseudouridine residues in large subunit ribosomal RNAs from representative eukaryotes, prokaryotes, archaebacteria, mitochondria and chloroplasts. J. Mol. Biol. 266, 246–268 (1997).

    Article  CAS  Google Scholar 

  29. Dominissini, D. et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201–206 (2012).

    Article  CAS  Google Scholar 

  30. Meyer, K. D. et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149, 1635–1646 (2012).

    Article  CAS  Google Scholar 

  31. Wang, X. et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505, 117–120 (2014).

    Article  Google Scholar 

  32. Meier, U. T. Dissecting dyskeratosis. Nat. Genet. 33, 116–117 (2003).

    Article  CAS  Google Scholar 

  33. Ruggero, D. et al. Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science 299, 259–262 (2003).

    Article  CAS  Google Scholar 

  34. Bellodi, C. et al. H/ACA small RNA dysfunctions in disease reveal key roles for noncoding RNA modifications in hematopoietic stem cell differentiation. Cell Rep. 3, 1493–1502 (2013).

    Article  CAS  Google Scholar 

  35. Mitchell, J. R., Wood, E. & Collins, K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402, 551–555 (1999).

    Article  CAS  Google Scholar 

  36. Bellodi, C. et al. Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. Cancer Res. 70, 6026–6035 (2010).

    Article  CAS  Google Scholar 

  37. Bykhovskaya, Y., Casas, K., Mengesha, E., Inbal, A. & Fischel-Ghodsian, N. Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). Am. J. Hum. Genet. 74, 1303–1308 (2004).

    Article  CAS  Google Scholar 

  38. Murray, J. L., Sheng, J. & Rubin, D. H. A role for H/ACA and C/D small nucleolar RNAs in viral replication. Mol. Biotechnol. 56, 429–437 (2014).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank members of the Yu laboratory for insightful discussions.

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Authors and Affiliations

  1. John Karijolich is at the Department of Plant and Microbial Biology, University of California, 565 Li Ka Shing Center #3370, Berkeley, California 94720-337, USA.,

    John Karijolich

  2. Chengqi Yi is at the State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Synthetic and Functional Biomolecules Center and Peking-Tsinghua Center for Life Sciences, Peking University, 5 Summer Palace Road, Haidian District, Beijing 100871, China.,

    Chengqi Yi

  3. Yi-Tao Yu is at the Department of Biochemistry and Biophysics, University of Rochester Medical Center, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712 Rochester, New York 14642, USA.,

    Yi-Tao Yu

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  1. John Karijolich
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Correspondence to John Karijolich or Yi-Tao Yu.

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Karijolich, J., Yi, C. & Yu, YT. Transcriptome-wide dynamics of RNA pseudouridylation. Nat Rev Mol Cell Biol 16, 581–585 (2015). https://doi.org/10.1038/nrm4040

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