Dynamic m6A modification and its emerging regulatory role in mRNA splicing

Science Bulletin

Volumn 60, Issue 1, 2015, Pages 21-32

  Yang, Ying ^a   Sun, Bao Fa ^a   Xiao, Wen ^a,b   Yang, Xin ^a,b   Sun, Hui Ying ^a,b,c   Zhao, Yong Liang ^a   Yang, Yun Gui ^a  

^a Chinese Academy of Sciences and China National Center for Bioinformation   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^c Sino Danish Center for Science and Education   (China)

Author keywords

Demethylase; M6A binding protein; Methyltransferase; mRNA splicing; N6 Methyl adenosine (M6A)

Indexed keywords

EID: 84941091151     PISSN: 20959273     EISSN: 20959281     Source Type: Journal    
DOI: 10.1007/s11434-014-0695-6     Document Type: Review

References (108)

1. Cantara WA, Crain PF, Rozenski J et al (2011) The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Res 39:D195–D201
2. Machnicka MA, Milanowska K, Oglou OO et al (2013) MODOMICS: a database of RNA modification pathways—2013 update. Nucleic Acids Res 41:D262–D267
3. Motorin Y, Helm M (2011) RNA nucleotide methylation. Wiley Interdiscip Rev RNA 2:611–631
4. 6-methyladenosine in the Rous sarcoma virus genome. J Mol Biol 113:165–179
5. 6-methyladenosine and 5′-terminal 7-methylguanosine in cap structures. J Virol 20:45–53
6. Rottman FM, Desrosiers RC, Friderici K (1976) Nucleotide methylation patterns in eukaryotic mRNA. Prog Nucleic Acid Res Mol Biol 19:21–38
7. Schibler U, Kelley DE, Perry RP (1977) Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. J Mol Biol 115:695–714
8. Srikantan S, Tominaga K, Gorospe M (2012) Functional interplay between RNA-binding protein HuR and microRNAs. Curr Protein Pept Sci 13:372–379
9. 6-methyladenosine sites of HeLa cell messenger ribonucleic acid. Biochemistry 16:1672–1676
10. Bokar JA (2005) The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA. In: Grosjean H (ed) Fine-tuning of RNA functions by modification and editing. Springer, Berlin, pp 141–177
11. Dubin DT, Taylor RH (1975) The methylation state of poly A-containing messenger RNA from cultured hamster cells. Nucleic Acids Res 2:1653–1668
12. Perry RP, Kelley DE, Friderici K et al (1975) The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5′ terminus. Cell 4:387–394
13. Wei CM, Gershowitz A, Moss B (1975) Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA. Cell 4:379–386
14. Rottman F, Shatkin AJ, Perry RP (1974) Sequences containing methylated nucleotides at the 5′ termini of messenger RNAs: possible implications for processing. Cell 3:197–199
15. 6-methyladenosine containing sequences in simian virus 40 RNA. Nucleic Acids Res 6:2879–2899
16. 6-adenosine methyltransferase. J Biol Chem 265:20117–20122
17. 6-adenosine methylase in vitro. Nucleic Acids Res 18:5735–5741
18. 6-methyladenosine residues in bovine prolactin mRNA. Proc Natl Acad Sci USA 81:5667–5671
19. 6-Adenosine methylation in mRNA: substrate specificity and enzyme complexity. Biochimie 76:1109–1114
20. Meyer KD, Saletore Y, Zumbo P et al (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635–1646
21. 6A-seq. Nature 485:201–206
22. Fustin JM, Doi M, Yamaguchi Y et al (2013) RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155:793–806
23. Schwartz S, Agarwala SD, Mumbach MR et al (2013) High-Resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell 155:1409–1421
24. 6-Methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol 16:191–198
25. 6-Methyl-adenosine modification in messenger and long non-coding RNA. Trends Biochem Sci 38:204–209
26. 6A) in RNA: an old modification with a novel epigenetic function. Genomics Proteomics Bioinf 11:8–17
27. 6A RNA methylation. Nat Rev Genet 15:293–306
28. Meyer KD, Jaffrey SR (2014) The dynamic epitranscriptome: N-methyladenosine and gene expression control. Nat Rev Mol Cell Biol 15:313–326
29. 6A and U-tail. Cell 158:980–987
30. Nilsen TW (2014) Internal mRNA methylation finally finds functions. Science 343:1207–1208
31. 6-Methyladenosine-dependent regulation of messenger RNA stability. Nature 505:117–120
32. 6-adenosine)-methyltransferase. RNA 3:1233–1247
33. 6-adenosine methylation. Nat Chem Biol 10:93–95
34. Narayan P, Rottman FM (1988) An in vitro system for accurate methylation of internal adenosine residues in messenger RNA. Science 242:1159–1162
35. 6-methyladenosine methyltransferase. Cell Res 24:177–189
36. 6A writers reveals two distinct classes of mRNA methylation at Internal and 5′ sites. Cell Rep 8:284–296
37. 6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J Biol Chem 269:17697–17704
38. Tuck MT (1992) The formation of internal 6-methyladenine residues in eucaryotic messenger RNA. Int J Biochem 24:379–386
39. 6-adenosine methylation sites in prolactin mRNA. Nucleic Acids Res 22:419–426
40. 6A methyltransferase. J Mol Evol 55:431–444
41. 6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene. Nucleic Acids Res 30:4509–4518
42. Hongay CF, Orr-Weaver TL (2011) Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis. Proc Natl Acad Sci USA 108:14855–14860
43. Zhong S, Li H, Bodi Z et al (2008) MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell 20:1278–1288
44. Bodi Z, Zhong S, Mehra S et al (2012) Adenosine methylation in Arabidopsis mRNA is associated with the 3′ end and reduced levels cause developmental defects. Front Plant Sci 3:48
45. Bodi Z, Button JD, Grierson D et al (2010) Yeast targets for mRNA methylation. Nucleic Acids Res 38:5327–5335
46. Shah JC, Clancy MJ (1992) IME4, a gene that mediates MAT and nutritional control of meiosis in Saccharomyces cerevisiae. Mol Cell Biol 12:1078–1086
47. Havugimana PC, Hart GT, Nepusz T et al (2012) A census of human soluble protein complexes. Cell 150:1068–1081
48. Agarwala SD, Blitzblau HG, Hochwagen A et al (2012) RNA methylation by the MIS complex regulates a cell fate decision in yeast. PLoS Genet 8:e1002732
49. Horiuchi K, Kawamura T, Iwanari H et al (2013) Identification of Wilms’ tumor 1-associating protein complex and its role in alternative splicing and the cell cycle. J Biol Chem 288:33292–33302
50. Little NA, Hastie ND, Davies RC (2000) Identification of WTAP, a novel Wilms’ tumour 1-associating protein. Hum Mol Genet 9:2231–2239
51. Granadino B, Campuzano S, Sanchez L (1990) The Drosophila melanogaster fl(2)d gene is needed for the female-specific splicing of Sex-lethal RNA. EMBO J 9:2597–2602
52. Ortega A, Niksic M, Bachi A et al (2003) Biochemical function of female-lethal (2)D/Wilms’ tumor suppressor-1-associated proteins in alternative pre-mRNA splicing. J Biol Chem 278:3040–3047
53. Schibler U, Perry RP (1977) The 5′-termini of heterogeneous nuclear RNA: a comparison among molecules of different sizes and ages. Nucleic Acids Res 4:4133–4149
54. 6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 8:885–887
55. Zheng GQ, Dahl JA, Niu YM et al (2013) ALKBH5 Is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 49:18–29
56. Peters T, Ausmeier K, Ruther U (1999) Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome 10:983–986
57. Dina C, Meyre D, Gallina S et al (2007) Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39:724–726
58. Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894
59. Scuteri A, Sanna S, Chen WM et al (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3:e115
60. Boissel S, Reish O, Proulx K et al (2009) Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet 85:106–111
61. Gerken T, Girard CA, Tung YC et al (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318:1469–1472
62. Fischer J, Koch L, Emmerling C et al (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898
63. Gao X, Shin YH, Li M et al (2010) The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice. PLoS One 5:e14005
64. McMurray F, Church CD, Larder R et al (2013) Adult onset global loss of the fto gene alters body composition and metabolism in the mouse. PLoS Genet 9:e1003166
65. Church C, Moir L, McMurray F et al (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42:1086–1092
66. Sanchez-Pulido L, Andrade-Navarro MA (2007) The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily. BMC Biochem 8:23
67. Jia G, Yang CG, Yang S et al (2008) Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett 582:3313–3319
68. Hess ME, Hess S, Meyer KD et al (2013) The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat Neurosci 16:1042–1048
69. 6-formyladenosine in mammalian RNA. Nat Commun 4:1798
70. Baltz AG, Munschauer M, Schwanhausser B et al (2012) The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Mol Cell 46:674–690
71. Zheng G, Dahl JA, Niu Y et al (2013) Sprouts of RNA epigenetics: the discovery of mammalian RNA demethylases. RNA Biol 10:915–918
72. 6A RNA by the YTHDC1 YTH domain. Nat Chem Biol 10:927–929
73. Ingolia NT, Ghaemmaghami S, Newman JRS et al (2009) Genome-wide analysis in vivo of translation with nucleotide resolution using Ribosome profiling. Science 324:218–223
74. Sheth U, Parker R (2003) Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300:805–808
75. Wang X, He C (2014) Reading RNA methylation codes through methyl-specific binding proteins. RNA Biol 11:669–672
76. Hiriart E, Vavasseur A, Touat-Todeschini L et al (2012) Mmi1 RNA surveillance machinery directs RNAi complex RITS to specific meiotic genes in fission yeast. EMBO J 31:2296–2308
77. Nayler O, Hartmann AM, Stamm S (2000) The ER repeat protein YT521-B localizes to a novel subnuclear compartment. J Cell Biol 150:949–962
78. Zhang B, zur Hausen A, Orlowska-Volk M et al (2010) Alternative splicing-related factor YT521: an independent prognostic factor in endometrial cancer. Int J Gynecol Cancer 20:492–499
79. Hirschfeld M, Zhang B, Jaeger M et al (2014) Hypoxia-dependent mRNA expression pattern of splicing factor YT521 and its impact on oncological important target gene expression. Mol Carcinog 53:883–892
80. 6-methyladenosine RNA: a reader of methylated RNA. Nucleic Acids Res pii:gku1116
81. Luo S, Tong L (2014) Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. Proc Natl Acad Sci USA 111:13834–13839
82. Fanale D, Iovanna JL, Calvo EL et al (2014) Germline copy number variation in the YTHDC2 gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility? Expert Opin Ther Targets 18:841–850
83. Ma WJ, Cheng S, Campbell C et al (1996) Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein. J Biol Chem 271:8144–8151
84. Kedde M, Agami R (2008) Interplay between microRNAs and RNA-binding proteins determines developmental processes. Cell Cycle 7:899–903
85. Kundu P, Fabian MR, Sonenberg N et al (2012) HuR protein attenuates miRNA-mediated repression by promoting miRISC dissociation from the target RNA. Nucleic Acids Res 40:5088–5100
86. Filippova N, Yang XH, King P et al (2012) Phosphoregulation of the RNA-binding protein Hu antigen R (HuR) by Cdk5 affects centrosome function. J Biol Chem 287:32277–32287
87. Lebedeva S, Jens M, Theil K et al (2011) Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol Cell 43:340–352
88. Mukherjee N, Corcoran DL, Nusbaum JD et al (2011) Integrative regulatory mapping indicates that the RNA-binding protein HuR couples Pre-mRNA processing and mRNA stability. Mol Cell 43:327–339
89. Liu N, Pan T (2014) RNA epigenetics. Transl Res 165:28–35
90. Chen M, Manley JL (2009) Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Bio 10:741–754
91. Braunschweig U, Gueroussov S, Plocik AM et al (2013) Dynamic integration of splicing within gene regulatory pathways. Cell 152:1252–1269
92. Hoskins AA, Moore MJ (2012) The spliceosome: a flexible, reversible macromolecular machine. Trends Biochem Sci 37:179–188
93. Wahl MC, Will CL, Luhrmann R (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136:701–718
94. 6-Methyladenosine residues in an intron-specific region of prolactin pre-mRNA. Mol Cell Biol 10:4456–4465
95. 6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res 24:1403–1419
96. Kanopka A, Muhlemann O, Akusjarvi G (1996) Inhibition by SR proteins of splicing of a regulated adenovirus pre-mRNA. Nature 381:535–538
97. Gallego ME, Gattoni R, Stevenin J et al (1997) The SR splicing factors ASF/SF2 and SC35 have antagonistic effects on intronic enhancer-dependent splicing of the beta-tropomyosin alternative exon 6A. EMBO J 16:1772–1784
98. Jumaa H, Nielsen PJ (1997) The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation. EMBO J 16:5077–5085
99. Cowper AE, Caceres JF, Mayeda A et al (2001) Serine-arginine (SR) protein-like factors that antagonize authentic SR proteins and regulate alternative splicing. J Biol Chem 276:48908–48914
100. Shin C, Kleiman FE, Manley JL (2005) Multiple properties of the splicing repressor SRp38 distinguish it from typical SR proteins. Mol Cell Biol 25:8334–8343
101. Shin C, Manley JL (2002) The SR protein SRp38 represses splicing in M phase cells. Cell 111:407–417
102. Pandit S, Zhou Y, Shiue L et al (2013) Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing. Mol Cell 50:223–235
103. Zhou B, Han Z (2013) Crystallization and preliminary X-ray diffraction of the RNA demethylase ALKBH5. Acta Crystallogr Sect F Struct Biol Cryst Commun 69:1231–1234
104. Xu C, Liu K, Tempel W et al (2014) Structures of Human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N-6-methyladenosine RNA demethylation. J Biol Chem 289:17299–17311
105. Feng C, Liu Y, Wang G et al (2014) Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition. J Biol Chem 289:11571–11583
106. Cook KB, Kazan H, Zuberi K et al (2011) RBPDB: a database of RNA-binding specificities. Nucleic Acids Res 39:D301–D308
107. Li JH, Liu S, Zhou H et al (2014) starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res 42:D92–D97
108. 6-alkyladenosines. Nucleic Acids Res 31:4472–4480