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Annual Review of Genomics and Human Genetics

Volume 15, 2014

The Pivotal Regulatory Landscape of RNA Modifications

Abstract

Posttranscriptionally modified nucleosides in RNA play integral roles in the cellular control of biological information that is encoded in DNA. The modifications of RNA span all three phylogenetic domains (Archaea, Bacteria, and Eukarya) and are pervasive across RNA types, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and (less frequently) small nuclear RNA (snRNA) and microRNA (miRNA). Nucleotide modifications are also one of the most evolutionarily conserved properties of RNAs, and the sites of modification are under strong selective pressure. However, many of these modifications, as well as their prevalence and impact, have only recently been discovered. Here, we examine both labile and permanent modifications, from simple methylation to complex transcript alteration (RNA editing and intron retention); detail the models for their processing; and highlight remaining questions in the field of the epitranscriptome.

Keyword(s): epitranscriptome, m6A, ribonucleotide modifications, RNA editing
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2014-08-31
2024-04-19
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Literature Cited

  1. Alon S, Eisenberg E. 1.  2013. Identifying RNA editing sites in miRNAs by deep sequencing. Methods Mol. Biol. 1038:159–70 [Google Scholar]
  2. Alon S, Mor E, Vigneault F, Church GM, Locatelli F. 2.  et al. 2012. Systematic identification of edited microRNAs in the human brain. Genome Res. 22:1533–40 [Google Scholar]
  3. Balik A, Penn AC, Nemoda Z, Greger IH. 3.  2013. Activity-regulated RNA editing in select neuronal subfields in hippocampus. Nucleic Acids Res. 41:1124–34 [Google Scholar]
  4. Bangs JD, Crain PF, Hashizume T, McCloskey JA, Boothroyd JC. 4.  1992. Mass spectrometry of mRNA cap 4 from trypanosomatids reveals two novel nucleosides. J. Biol. Chem. 267:9805–15 [Google Scholar]
  5. Bass BL, Weintraub H. 5.  1987. A developmentally regulated activity that unwinds RNA duplexes. Cell 48:607–13 [Google Scholar]
  6. Bass BL, Weintraub H. 6.  1988. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55:1089–98 [Google Scholar]
  7. Beadle GW, Tatum EL. 7.  1941. Genetic control of biochemical reactions in Neurospora. Proc. Natl. Acad. Sci. USA 27:499–506 [Google Scholar]
  8. Benne R, Van den Burg J, Brakenhoff JP, Sloof P, Van Boom JH, Tromp MC. 8.  1986. Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell 46:819–26 [Google Scholar]
  9. Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayan P, Rottman F. 9.  1994. Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei: Internal mRNA methylation requires a multisubunit complex. J. Biol. Chem. 269:17697–704 [Google Scholar]
  10. Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM. 10.  et al. 2013. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494:366–70 [Google Scholar]
  11. Burns MB, Temiz NA, Harris RS. 11.  2013. Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat. Genet. 45:977–83 [Google Scholar]
  12. Cantara WA, Crain PF, Rozenski J, McCloskey JA, Harris KA. 12.  et al. 2011. The RNA Modification Database, RNAMDB: 2011 update. Nucleic Acids Res. 39:D195–201 [Google Scholar]
  13. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO. 13.  et al. 2012. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2:401–4 [Google Scholar]
  14. Chambers KF, Bacon JR, Kemsley EK, Mills RD, Ball RY. 14.  et al. 2009. Gene expression profile of primary prostate epithelial and stromal cells in response to sulforaphane or iberin exposure. Prostate 69:1411–21 [Google Scholar]
  15. Chandran UR, Ma C, Dhir R, Bisceglia M, Lyons-Weiler M. 15.  et al. 2007. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer 7:64 [Google Scholar]
  16. Chen L. 16.  2013. Characterization and comparison of human nuclear and cytosolic editomes. Proc. Natl. Acad. Sci. USA 110:E2741–47 [Google Scholar]
  17. Chen L, Li Y, Lin CH, Chan TH, Chow RK. 17.  et al. 2013. Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nat. Med. 19:209–16 [Google Scholar]
  18. Chester A, Somasekaram A, Tzimina M, Jarmuz A, Gisbourne J. 18.  et al. 2003. The apolipoprotein B mRNA editing complex performs a multifunctional cycle and suppresses nonsense-mediated decay. EMBO J. 22:3971–82 [Google Scholar]
  19. Cho DS, Yang W, Lee JT, Shiekhattar R, Murray JM, Nishikura K. 19.  2003. Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. J. Biol. Chem. 278:17093–102 [Google Scholar]
  20. Choudhury Y, Tay FC, Lam DH, Sandanaraj E, Tang C. 20.  et al. 2012. Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells. J. Clin. Investig. 122:4059–76 [Google Scholar]
  21. Chow LT, Gelinas RE, Broker TR, Roberts RJ. 21.  1977. An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell 12:1–8 [Google Scholar]
  22. Church C, Moir L, McMurray F, Girard C, Banks GT. 22.  et al. 2010. Overexpression of Fto leads to increased food intake and results in obesity. Nat. Genet. 42:1086–92 [Google Scholar]
  23. Conticello SG. 23.  2008. The AID/APOBEC family of nucleic acid mutators. Genome Biol. 9:229 [Google Scholar]
  24. Cowling VH. 24.  2010. Regulation of mRNA cap methylation. Biochem. J. 425:295–302 [Google Scholar]
  25. Crain PF, McCloskey JA. 25.  1996. The RNA modification database. Nucleic Acids Res. 24:98–99 [Google Scholar]
  26. Crain PF, McCloskey JA. 26.  1997. The RNA modification database. Nucleic Acids Res. 25:126–27 [Google Scholar]
  27. Dahm R. 27.  2008. Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. Hum. Genet. 122:565–81 [Google Scholar]
  28. Decatur WA, Fournier MJ. 28.  2003. RNA-guided nucleotide modification of ribosomal and other RNAs. J. Biol. Chem. 278:695–98 [Google Scholar]
  29. Desrosiers RC, Friderici KH, Rottman FM. 29.  1975. Characterization of Novikoff hepatoma mRNA methylation and heterogeneity in the methylated 5′ terminus. Biochemistry 14:4367–74 [Google Scholar]
  30. Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA. 30.  et al. 2013. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 503:371–76 [Google Scholar]
  31. Dominissini D, Amariglio N, Rechavi G. 31.  2012. Micro-editing mistake translates into a devastating brain tumor. J. Clin. Investig. 122:3842–45 [Google Scholar]
  32. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L. 32.  et al. 2012. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485:201–6 [Google Scholar]
  33. Dubin DT, Taylor RH. 33.  1975. The methylation state of poly A-containing messenger RNA from cultured hamster cells. Nucleic Acids Res. 2:1653–68 [Google Scholar]
  34. Ekdahl Y, Farahani HS, Behm M, Lagergren J, Ohman M. 34.  2012. A-to-I editing of microRNAs in the mammalian brain increases during development. Genome Res. 22:1477–87 [Google Scholar]
  35. Elkon R, Ugalde AP, Agami R. 35.  2013. Alternative cleavage and polyadenylation: extent, regulation and function. Nat. Rev. Genet. 14:496–506 [Google Scholar]
  36. Figueroa ME, Wouters BJ, Skrabanek L, Glass J, Li Y. 36.  et al. 2009. Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features. Blood 113:2795–804 [Google Scholar]
  37. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM. 37.  et al. 2007. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–94 [Google Scholar]
  38. Fu Y, He C. 38.  2012. Nucleic acid modifications with epigenetic significance. Curr. Opin. Chem. Biol. 16:516–24 [Google Scholar]
  39. Fu Y, Jia G, Pang X, Wang RN, Wang X. 39.  et al. 2013. FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat. Commun. 4:1798 [Google Scholar]
  40. Fustin JM, Doi M, Yamaguchi Y, Hida H, Nishimura S. 40.  et al. 2013. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155:793–806 [Google Scholar]
  41. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B. 41.  et al. 2013. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6pl1
  42. Gao M, Fritz DT, Ford LP, Wilusz J. 42.  2000. Interaction between a poly(A)-specific ribonuclease and the 5′ cap influences mRNA deadenylation rates in vitro. Mol. Cell 5:479–88 [Google Scholar]
  43. García-López J, Hourcade JDD, Del Mazo J. 43.  2013. Reprogramming of microRNAs by adenosine-to-inosine editing and the selective elimination of edited microRNA precursors in mouse oocytes and preimplantation embryos. Nucleic Acids Res. 41:5483–93 [Google Scholar]
  44. Garrett S, Rosenthal JJ. 44.  2012. RNA editing underlies temperature adaptation in K+ channels from polar octopuses. Science 335:848–51 [Google Scholar]
  45. Guenther UP, Yandek LE, Niland CN, Campbell FE, Anderson D. 45.  et al. 2013. Hidden specificity in an apparently nonspecific RNA-binding protein. Nature 502:385–88 [Google Scholar]
  46. He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R. 46.  et al. 2005. The role of microRNA genes in papillary thyroid carcinoma. Proc. Natl. Acad. Sci. USA 102:19075–80 [Google Scholar]
  47. Horowitz S, Horowitz A, Nilsen TW, Munns TW, Rottman FM. 47.  1984. Mapping of N6-methyladenosine residues in bovine prolactin mRNA. Proc. Natl. Acad. Sci. USA 81:5667–71 [Google Scholar]
  48. HsuChen CC, Dubin DT. 48.  1976. Di-and trimethylated congeners of 7-methylguanine in Sindbis virus mRNA. Nature 264:190–91 [Google Scholar]
  49. Iwanami Y, Brown GM. 49.  1968. Methylated bases of ribosomal ribonucleic acid from HeLa cells. Arch. Biochem. Biophys. 126:8–15 [Google Scholar]
  50. Iwanami Y, Brown GM. 50.  1968. Methylated bases of transfer ribonucleic acid from HeLa and L cells. Arch. Biochem. Biophys. 124:472–82 [Google Scholar]
  51. Jia G, Fu Y, He C. 51.  2013. Reversible RNA adenosine methylation in biological regulation. Trends Genet. 29:108–15 [Google Scholar]
  52. Jia G, Fu Y, Zhao X, Dai Q, Zheng G. 52.  et al. 2011. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7:885–87 [Google Scholar]
  53. Jia G, Yang CG, Yang S, Jian X, Yi C. 53.  et al. 2008. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 582:3313–19 [Google Scholar]
  54. Johnson TB, Coghill RDW. 54.  1925. Researches on pyrimidines. C111. The discovery of 5-methyl-cytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus. J. Am. Chem. Soc. 47:2838–44 [Google Scholar]
  55. Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E. 55.  et al. 2012. miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 72:1865–77 [Google Scholar]
  56. Kawahara Y. 56.  2012. Quantification of adenosine-to-inosine editing of microRNAs using a conventional method. Nat. Protoc. 7:1426–37 [Google Scholar]
  57. Kawahara Y, Zinshteyn B, Chendrimada TP, Shiekhattar R, Nishikura K. 57.  2007. RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep. 8:763–69 [Google Scholar]
  58. Kellinger MW, Song CX, Chong J, Lu XY, He C, Wang D. 58.  2012. 5-Formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription. Nat. Struct. Mol. Biol. 19:831–33 [Google Scholar]
  59. Kiran AM, Baranov PV. 59.  2010. DARNED: a DAtabase of RNa EDiting in humans. Bioinformatics 26:1772–76 [Google Scholar]
  60. Kiran AM, O'Mahony JJ, Sanjeev K, Baranov PV. 60.  2013. Darned in 2013: inclusion of model organisms and linking with Wikipedia. Nucleic Acids Res. 41:D258–61 [Google Scholar]
  61. Kurowski MA, Bhagwat AS, Papaj G, Bujnicki JM. 61.  2003. Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB. BMC Genomics 4:48 [Google Scholar]
  62. Lagana A, Paone A, Veneziano D, Cascione L, Gasparini P. 62.  et al. 2012. miR-EdiTar: a database of predicted A-to-I edited miRNA target sites. Bioinformatics 28:3166–68 [Google Scholar]
  63. Laurencikiene J, Kallman AM, Fong N, Bentley DL, Ohman M. 63.  2006. RNA editing and alternative splicing: the importance of co-transcriptional coordination. EMBO Rep. 7:303–7 [Google Scholar]
  64. Lavrov DV, Brown WM, Boore JL. 64.  2000. A novel type of RNA editing occurs in the mitochondrial tRNAs of the centipede Lithobius forficatus. Proc. Natl. Acad. Sci. USA 97:13738–42 [Google Scholar]
  65. Li M, Wang IX, Li Y, Bruzel A, Richards AL. 65.  et al. 2011. Widespread RNA and DNA sequence differences in the human transcriptome. Science 333:53–58 [Google Scholar]
  66. Li S, Tighe SW, Nicolet CM, Grove D, Levy S. 66.  et al. 2014. Multi-platform and cross-methodological reproducibility of transcriptome profiling by RNA-seq in the ABRF Next-Generation Sequencing Study (ABRF-NGS). Nat. Biotechnol. In press
  67. Limbach PA, Crain PF, McCloskey JA. 67.  1994. Summary: the modified nucleosides of RNA. Nucleic Acids Res. 22:2183–96 [Google Scholar]
  68. Liou RF, Blumenthal T. 68.  1990. Trans-spliced Caenorhabditis elegans mRNAs retain trimethylguanosine caps. Mol. Cell. Biol. 10:1764–68 [Google Scholar]
  69. Liu J, Yue Y, Han D, Wang X, Fu Y. 69.  et al. 2014. A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10:93–95 [Google Scholar]
  70. Liu N, Parisien M, Dai Q, Zheng G, He C, Pan T. 70.  2013. Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA. RNA 19:1848–56 [Google Scholar]
  71. Marín-Béjar O, Marchese FP, Athie A, Sánchez Y, González J. 71.  et al. 2013. Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2. Genome Biol. 14:R104 [Google Scholar]
  72. Mayr C, Bartel DP. 72.  2009. Widespread shortening of 3′ UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138:673–84 [Google Scholar]
  73. Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C. 73.  et al. 2012. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat. Biotechnol. 30:99–104 [Google Scholar]
  74. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. 74.  2012. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635–46 [Google Scholar]
  75. Mower JP. 75.  2008. Modeling sites of RNA editing as a fifth nucleotide state reveals progressive loss of edited sites from angiosperm mitochondria. Mol. Biol. Evol. 25:52–61 [Google Scholar]
  76. Nemlich Y, Greenberg E, Ortenberg R, Besser MJ, Barshack I. 76.  et al. 2013. MicroRNA-mediated loss of ADAR1 in metastatic melanoma promotes tumor growth. J. Clin. Investig. 123:2703–18 [Google Scholar]
  77. Nishikura K. 77.  2010. Functions and regulation of RNA editing by ADAR deaminases. Annu. Rev. Biochem. 79:321–49 [Google Scholar]
  78. Ota H, Sakurai M, Gupta R, Valente L, Wulff BE. 78.  et al. 2013. ADAR1 forms a complex with Dicer to promote microRNA processing and RNA-induced gene silencing. Cell 153:575–89 [Google Scholar]
  79. Park E, Williams B, Wold BJ, Mortazavi A. 79.  2012. RNA editing in the human ENCODE RNA-seq data. Genome Res. 22:1626–33 [Google Scholar]
  80. Pasquinelli AE. 80.  2012. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat. Rev. Genet. 13:271–82 [Google Scholar]
  81. Paz-Yaacov N, Levanon EY, Nevo E, Kinar Y, Harmelin A. 81.  et al. 2010. Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proc. Natl. Acad. Sci. USA 107:12174–79 [Google Scholar]
  82. Peng Z, Cheng Y, Tan BC, Kang L, Tian Z. 82.  et al. 2012. Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome. Nat. Biotechnol. 30:253–60 [Google Scholar]
  83. Penn AC, Balik A, Greger IH. 83.  2013. Steric antisense inhibition of AMPA receptor Q/R editing reveals tight coupling to intronic editing sites and splicing. Nucleic Acids Res. 41:1113–23 [Google Scholar]
  84. Perry RP, Kelley DE, Friderici K, Rottman F. 84.  1975. The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5′ terminus. Cell 4:387–94 [Google Scholar]
  85. Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J. 85.  1987. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell 50:831–40 [Google Scholar]
  86. Ramaswami G, Li JB. 86.  2014. RADAR: a rigorously annotated database of A-to-I RNA editing. Nucleic Acids Res. 42:D109–113 [Google Scholar]
  87. Rebagliati MR, Melton DA. 87.  1987. Antisense RNA injections in fertilized frog eggs reveal an RNA duplex unwinding activity. Cell 48:599–605 [Google Scholar]
  88. Rieder LE, Staber CJ, Hoopengardner B, Reenan RA. 88.  2013. Tertiary structural elements determine the extent and specificity of messenger RNA editing. Nat. Commun. 4:2232 [Google Scholar]
  89. Rueter SM, Dawson TR, Emeson RB. 89.  1999. Regulation of alternative splicing by RNA editing. Nature 399:75–80 [Google Scholar]
  90. Saletore Y, Chen-Kiang S, Mason CE. 90.  2013. Novel RNA regulatory mechanisms revealed in the epitranscriptome. RNA Biol. 10:342–46 [Google Scholar]
  91. Saletore Y, Meyer K, Korlach J, Vilfan ID, Jaffrey S, Mason CE. 91.  2012. The birth of the epitranscriptome: deciphering the function of RNA modifications. Genome Biol. 13:175 [Google Scholar]
  92. Sanchez-Palencia A, Gomez-Morales M, Gomez-Capilla JA, Pedraza V, Boyero L. 92.  et al. 2011. Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer. Int. J. Cancer. 129:355–64 [Google Scholar]
  93. Scadden AD. 93.  2005. The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage. Nat. Struct. Mol. Biol. 12:489–96 [Google Scholar]
  94. Schaefer M, Pollex T, Hanna K, Lyko F. 94.  2009. RNA cytosine methylation analysis by bisulfite sequencing. Nucleic Acids Res. 37e12
  95. Schibler U, Kelley DE, Perry RP. 95.  1977. Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. J. Mol. Biol. 115:695–714 [Google Scholar]
  96. Schwartz S, Agarwala SD, Mumbach MR, Jovanovic M, Mertins P. 95a.  et al. 2014. High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell 155:14091–21 [Google Scholar]
  97. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y. 96.  et al. 2007. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–45 [Google Scholar]
  98. Simon JM, Hacker KE, Singh D, Brannon AR, Parker JS. 97.  et al. 2014. Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects. Genome Res. 24:241–50 [Google Scholar]
  99. Smith RM, Webb A, Papp AC, Newman LC, Handelman SK. 98.  et al. 2013. Whole transcriptome RNA-Seq allelic expression in human brain. BMC Genomics 14:571 [Google Scholar]
  100. Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT. 99.  et al. 2012. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 40:5023–33 [Google Scholar]
  101. St Laurent G, Tackett MR, Nechkin S, Shtokalo D, Antonets D. 100.  et al. 2013. Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila. Nat. Struct. Mol. Biol. 20:1333–39 [Google Scholar]
  102. Su Z, Łabaj P, Li S, Thierry-Mieg J, Thierry-Mieg D. 101.  et al. 2014. Power and limitations of RNA-seq: findings from the SEQC (MAQC-III) consortium. Nat. Biotechnol. In press
  103. Traka M, Gasper AV, Melchini A, Bacon JR, Needs PW. 102.  et al. 2008. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS ONE 3:e2568 [Google Scholar]
  104. Tschudi C, Ullut E. 103.  2002. Unconventional rules of small nuclear RNA transcription and cap modification in trypanosomatids. Gene Expr. 10:3–16 [Google Scholar]
  105. Varambally S, Yu J, Laxman B, Rhodes DR, Mehra R. 104.  et al. 2005. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell 8:393–406 [Google Scholar]
  106. Veliz EA, Easterwood LM, Beal PA. 105.  2003. Substrate analogues for an RNA-editing adenosine deaminase: mechanistic investigation and inhibitor design. J. Am. Chem. Soc. 125:10867–76 [Google Scholar]
  107. Vicente-Dueñas C, Fontán L, Gonzalez-Herrero I, Romero-Camarero I, Segura V. 106.  et al. 2012. Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice. Proc. Natl. Acad. Sci. USA 109:10534–39 [Google Scholar]
  108. Vilfan ID, Tsai YC, Clark TA, Wegener J, Dai Q. 107.  et al. 2013. Analysis of RNA base modification and structural rearrangement by single-molecule real-time detection of reverse transcription. J. Nanobiotechnol. 11:8 [Google Scholar]
  109. Wagner RW, Smith JE, Cooperman BS, Nishikura K. 108.  1989. A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc. Natl. Acad. Sci. USA 86:2647–51 [Google Scholar]
  110. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L. 109.  et al. 2008. Alternative isoform regulation in human tissue transcriptomes. Nature 456:470–76 [Google Scholar]
  111. Wang IX, So E, Devlin JL, Zhao Y, Wu M, Cheung VG. 110.  2013. ADAR regulates RNA editing, transcript stability, and gene expression. Cell Rep. 5:849–60 [Google Scholar]
  112. Wang Q, Hui H, Guo Z, Zhang W, Hu Y. 111.  et al. 2013. ADAR1 regulates ARHGAP26 gene expression through RNA editing by disrupting miR-30b-3p and miR-573 binding. RNA 19:1525–36 [Google Scholar]
  113. Wang X, Lu Z, Gomez A, Hon GC, Yue Y. 112.  et al. 2014. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505:117–20 [Google Scholar]
  114. Wang Y, Li Y, Toth JI, Petrosky MD, Zhang Z, Zhao JC. 112a.  2014. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16:191–98 [Google Scholar]
  115. Wang Z, Burge CB. 113.  2008. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 14:802–13 [Google Scholar]
  116. Wei CM, Gershowitz A, Moss B. 114.  1975. Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA. Cell 4:379–86 [Google Scholar]
  117. Woese CR. 115.  1967. The Genetic Code: The Molecular Basis for Genetic Expression New York: Harper and Row
  118. Wong JJ, Ritchie W, Ebner OA, Selbach M, Wong JW. 116.  et al. 2013. Orchestrated intron retention regulates normal granulocyte differentiation. Cell 154:583–95 [Google Scholar]
  119. Wu AR, Neff NF, Kalisky T, Dalerba P, Treutlein B. 117.  et al. 2014. Quantitative assessment of single-cell RNA-sequencing methods. Nat. Methods 11:41–46 [Google Scholar]
  120. Xhemalce B, Robson SC, Kouzarides T. 118.  2012. Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell 151:278–88 [Google Scholar]
  121. Yang W, Chendrimada TP, Wang Q, Higuchi M, Seeburg PH. 119.  et al. 2006. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat. Struct. Mol. Biol. 13:13–21 [Google Scholar]
  122. Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM. 120.  et al. 2013. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49:18–29 [Google Scholar]
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The Pivotal Regulatory Landscape of RNA Modifications
Annual Review of Genomics and Human Genetics 15, 127 (2014); https://doi.org/10.1146/annurev-genom-090413-025405
/content/journals/10.1146/annurev-genom-090413-025405
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