Molecular Biology

, Volume 49, Issue 6, pp 825–836 | Cite as

Posttranscriptional modification of messenger RNAs in eukaryotes

  • I. G. Laptev
  • A. Ya. Golovina
  • P. V. Sergiev
  • O. A. Dontsova


Transcriptome-wide mapping of posttranscriptional modifications in eukaryotic RNA revealed tens of thousands of modification sites. Modified nucleotides include 6-methyladenosine, 5-methylcytidine, pseudouridine, inosine, etc. Many modification sites are conserved, and many are regulated. The function is known for a minor subset of modified nucleotides, while the role of their majority is still obscure. In view of the global character of mRNA modification, RNA epigenetics arose as a new field of molecular biology. The review considers posttranscriptional modification of eukaryotic mRNA, focusing on the major modified nucleotides, the role they play in the cell, the methods to detect them, and the enzymes responsible for modification.


6-methyladenosine 5-methylcytidine pseuouridine inosine 


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  1. 1.
    Dominissini D., Moshitch-Moshkovitz S., Schwartz S., et al. 2012. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 485, 201–206.PubMedCrossRefGoogle Scholar
  2. 2.
    Meyer K.D., 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.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Squires J.E., Patel H.R., Nousch M., et al. 2012. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 40, 5023–5033.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Carlile T.M., Rojas-Duran M.F., Zinshteyn B., et al. 2014. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature. 515, 143–146.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Schwartz S., Bernstein D.A., Mumbach M.R., et al. 2014. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell. 159, 148–162.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Lovejoy A.F., Riordan D.P., Brown P.O. 2014. Transcriptome-wide mapping of pseudouridines: pseudouridine synthases modify specific mRNAs in S. cerevisiae. PLOS ONE. 9, e110799.Google Scholar
  7. 7.
    Muthukrishnan S., Both G.W., Furuichi Y., et al. 1975. 5'-Terminal 7-methylguanosine in eukaryotic mRNA is required for translation. Nature. 255, 33–37.PubMedCrossRefGoogle Scholar
  8. 8.
    Wei C.M., Gershowitz A., Moss B. 1975. Methylated nucleotides block 5' terminus of HeLa cell messenger RNA. Cell. 4, 379–386.PubMedCrossRefGoogle Scholar
  9. 9.
    Murthy M.R. 1982. Blocked and methylated 5'-terminal cap structures of rat brain messenger ribonucleic acids. J. Neurochem. 38, 28–40.CrossRefGoogle Scholar
  10. 10.
    Langberg S.R., Moss B. 1981. Post-transcriptional modifications of mRNA. Purification and characterization of cap I and cap II RNA (nucleoside-2'-)methyltransferases from HeLa cells. J. Biol. Chem. 256, 10054–10060.PubMedGoogle Scholar
  11. 11.
    Werner M., Purta E., Kaminska K.H., et al. 2011. 2'-O-ribose methylation of cap2 in human: Function and evolution in a horizontally mobile family. Nucleic Acids Res. 39, 4756–4768.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Daffis S., Szretter K.J., Schriewer J., et al. 2010. 2'-O-methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature. 468, 452–456.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Züst R., Cervantes-Barragan L., Habjan M., et al. 2011. Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat. Immunol. 12, 137–143.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Desrosiers R., Friderici K., Rottman F. 1974. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc. Natl. Acad. Sci. U. S. A. 71, 3971–3975.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Horowitz S., Horowitz A., Nilsen T.W., et al. 1984. Mapping of N6-methyladenosine residues in bovine prolactin mRNA. Proc. Natl. Acad. Sci. U. S. A. 81, 5667–5671.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Narayan P., Ludwiczak R.L., Goodwin E.C., et al. 1994. Context effects on N6-adenosine methylation sites in prolactin mRNA. Nucleic Acids Res. 22, 419–426.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Kane S.E., Beemon K. 1985. Precise localization of m6A in Rous sarcoma virus RNA reveals clustering of methylation sites: Implications for RNA processing. Mol. Cell. Biol. 5, 2298–2306.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Shibler U., Kelley D.E., Perry R.P. 1997. Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. J. Mol. Biol. 115, 695–714.CrossRefGoogle Scholar
  19. 19.
    Schwartz S., Agarwala S.D., Mumbach M.R., et al. 2013. High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell. 155, 1409–1421.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Vilfan I.D., Tsai Y.-C., Clark T.A., et al. 2013. Analysis of RNA base modification and structural rearrangement by single-molecule real-time detection of reverse transcription. J. Nanobiotechnol. 11, 8.CrossRefGoogle Scholar
  21. 21.
    Harcourt E.M., Ehrenschwender T., Batista P.J., et al. 2013. Identification of a selective polymerase enables detection of N6-methyladenosine in RNA. J. Am. Chem. Soc. 135, 19079–19082.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Golovina A.Y., Dzama M.M., Petriukov K.S., et al. 2014. Method for site-specific detection of m6A nucleoside presence in RNA based on high-resolution melting (HRM) analysis. Nucleic Acids Res. 42, e27.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Liu N., Parisien M., Dai Q., et al. 2013. Probing N6methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA. RNA. 19, 1848–1856.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Bokar J.A., Shambaugh M.E., Polayes D., et al. 1997. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenisine)methyltransferase. RNA. 3 (11), 1233–1247.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Liu N., Pan T. 2015. RNA epigenetics. Transl. Res. 165, 28–35.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Liu J., Yue Y., Han D., et al. 2013. A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10, 93–95.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Ping X.-L., Sun B.-F., Wang L., et al. 2014. Mammalian WTAP is a regulatory subunit of the RNA N6methyladenosine methyltransferase. Cell Res. 24, 177–189.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Horiuchi K., Umetani M., Minami T., et al. 2006. Wilms’ tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc. Natl. Acad. Sci. U. S. A. 103, 17278–17283.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Gerken T., Girard C.A., Tung Y.-C.L., et al. 2007. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 318, 1469–1472.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Jia G., Yang C.-G., 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.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Jia G., Fu Y., Zhao X., et al. 2011. N6-methyladenosine in nuclear RNA is a major substrate of the obesityassociated FTO. Nat. Chem. Biol. 7, 885–887.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Boissel S., Reish O., Proulx K., et al. 2009. Loss-offunction mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am. J. Hum. Genet. 85, 106–111.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Han Z., Niu T., Chang J., et al. 2010. Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature. 464, 1205–1209.PubMedCrossRefGoogle Scholar
  34. 34.
    Ratel D., Ravanat J.-L., Charles M.-P., et al. 2006. Undetectable levels of N6-methyl adenine in mouse DNA: cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase. FEBS Lett. 580, 3179–3184.PubMedCrossRefGoogle Scholar
  35. 35.
    Fu Y., Jia G., Pang X., et al. 2013. FTO-mediated formation of N6-hydroxymethyladenosine and N6formyladenosine in mammalian RNA. Nat. Commun. 4, 1798.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Zheng G., Dahl J.A., Niu Y., et al. 2013. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell. 49, 18–29.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Ma W.-J., Cheng S., Campbell C., et al. 1996. Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein. J. Biol. Chem. 271, 8144–8151.PubMedCrossRefGoogle Scholar
  38. 38.
    Kedde M., Agami R. 2008. Interplay between microRNAs and RNA-binding proteins determines developmental processes. Cell Cycle. 7, 899–903.PubMedCrossRefGoogle Scholar
  39. 39.
    Kundu P., Fabian M.R., 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.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Wang Y., Li Y., Toth J.I., et al. 2014. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16, 191–198.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Stoilov P., Rafalska I., Stamm S. 2002. YTH: A new domain in nuclear proteins. Trends Biochem. Sci. 27, 495–497.PubMedCrossRefGoogle Scholar
  42. 42.
    Wang X., Lu Z., Gomez A., et al. 2013. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 505, 117–120.PubMedCrossRefGoogle Scholar
  43. 43.
    Batista P.J., Molinie B., Wang J., et al. 2014. m6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell. 15, 707–719.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Geula S., Moshitch-Moshkovitz S., Dominissini D., et al. 2015. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science. 347, 1002–1006.PubMedCrossRefGoogle Scholar
  45. 45.
    Dubin D.T., Taylor R.H. 1975. The methylation state of poly A-containing-messenger RNA from cultured hamster cells. Nucleic Acids Res. 2, 1653–1668.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Dubin D.T., Stollar V. 1975. Methylation of Sindbis virus “26S” messenger RNA. Biochem. Biophys. Res. Commun. 66, 1373–1379.PubMedCrossRefGoogle Scholar
  47. 47.
    Sommer R., Salditt-Georgieff M., Bachenheimer S., et al. 1976. The methylation of adenovirus-specific nuclear and cytoplasmic RNA. Nucleic Acids Res. 3, 749–765.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Furuichi Y., Morgan M., Shatkin A.J., et al. 1975. Methylated, blocked 5 termini in HeLa cell mRNA. Proc. Natl. Acad. Sci. U. S. A. 72, 1904–1908.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Hussain S., Sajini A.A., Blanco S., et al. 2013. NSun2mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Rep. 4, 255–261.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Frye M., Watt F.M. 2006. The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Curr. Biol. 16, 971–981.PubMedCrossRefGoogle Scholar
  51. 51.
    Brzezicha B., Schmidt M., Makalowska I., et al. 2006. Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the Formula. Nucleic Acids Res. 34, 6034–6043.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Hussain S., Tuorto F., Menon S., et al. 2013. The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation. Mol. Cell. Biol. 33, 1561–1570.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Blanco S., Kurowski A., Nichols J., et al. 2011. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS Genet. 7, 1–14.CrossRefGoogle Scholar
  54. 54.
    Khoddami V., Cairns B.R. 2013. Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nat. Biotechnol. 31, 458–464.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Gu W., Hurto R.L., Hopper A.K., et al. 2005. Depletion of Saccharomyces cerevisiae tRNAHis guanylyltransferase Thg1p leads to uncharged tRNAHis with additional m5C. Mol. Cell. Biol. 25, 8191–8201.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Eckhardt F., Lewin J., Cortese R., et al. 2006. DNA methylation profiling of human chromosomes 6, 20, and 22. Nat. Genet. 38, 1378–1385.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    King M.Y., Redman K.L. 2002. RNA methyltransferases utilize two cysteine residues in the formation of 5-methylcytosine. Biochemistry. 41, 11218–11225.PubMedCrossRefGoogle Scholar
  58. 58.
    Jackson-Grusby L., Laird P.W., Magge S.N., et al. 1997. Mutagenicity of 5-aza-2'-deoxycytidine is mediated by the mammalian DNA methyltransferase. Proc. Natl. Acad. Sci. U. S. A. 94, 4681–4685.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Hussain S., Benavente S.B., Nascimento E., et al. 2009. The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle stability. J. Cell Biol. 186, 27–40.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Agris P.F. 2008. Bringing order to translation: The contributions of transfer RNA anticodon-domain modifications. EMBO Rep. 9, 629–635.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Basti M.M., Stuart J.W., Lam A.T., et al. 1996. Design, biological activity and NMR-solution structure of a DNA analogue of yeast tRNAPhe anticodon domain. Nat. Struct. Biol. 3, 38–44.PubMedCrossRefGoogle Scholar
  62. 62.
    Chow C.S., Lamichhane T.N., Mahto S.K. 2007. Expanding the nucleotide repertoire of the ribosome with post-transcriptional modifications. ACS Chem. Biol. 2, 610–619.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Amort T., Soulière M.F., Wille A., et al. 2013. Long non-coding RNAs as targets for cytosine methylation. RNA Biol. 10, 1002–1008.PubMedCentralCrossRefGoogle Scholar
  64. 64.
    Davis F.F., Allen F.W. 1957. Ribonucleic acids from yeast which contain a fifth nucleotide. J. Biol. Chem. 227, 907–915.PubMedGoogle Scholar
  65. 65.
    Ge J., Yu Y.-T. 2013. RNA pseudouridylation: new insights into an old modification. Trends Biochem. Sci. 38, 210–218.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Hoang C., Ferré-D’Amaré A.R. 2001. Cocrystal structure of a tRNA ψ55 pseudouridine synthase: Nucleotide flipping by an RNA-modifying enzyme. Cell. 107, 929–939.PubMedCrossRefGoogle Scholar
  67. 67.
    Ni J., Tien A.L., Fournier M.J. 1997. Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell. 89, 565–573.PubMedCrossRefGoogle Scholar
  68. 68.
    Baker D.L. 2005. RNA-guided RNA modification: functional organization of the archaeal H/ACA RNP. Genes Dev. 19, 1238–1248.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Ma X., Yang C., Alexandrov A., et al. 2005. Pseudouridylation of yeast U2 snRNA is catalyzed by either an RNA-guided or RNA-independent mechanism. EMBO J. 24, 2403–2413.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Xiao M., Yang C., Schattner P., et al. 2008. Functionality and substrate specificity of human box H/ACA guide RNAs. RNA. 15, 176–186.PubMedCrossRefGoogle Scholar
  71. 71.
    Massenet S., Motorin Y., Lafontaine D.L., et al. 1999. Pseudouridine mapping in the Saccharomyces cerevisiae spliceosomal U small nuclear RNAs (snRNAs) reveals that pseudouridine synthase pus1p exhibits a dual substrate specificity for U2 snRNA and tRNA. Mol. Cell. Biol. 19, 2142–2154.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Ma X., Zhao X., Yu Y.-T. 2003. Pseudouridylation (ψ) of U2 snRNA in S.cerevisiae is catalyzed by an RNAindependent mechanism. EMBO J. 22, 1889–1897.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Cavaillé J., Buiting K., Kiefmann M., et al. 2000. Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc. Natl. Acad. Sci. U. S. A. 97, 14311–14316.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Hüttenhofer A., Brosius J., Bachellerie J.-P. 2002. RNomics: Identification and function of small, nonmessenger RNAs. Curr. Opin. Chem. Biol. 6, 835–843.PubMedCrossRefGoogle Scholar
  75. 75.
    Hunter S., Jones P., Mitchell A., et al. 2012. InterPro in 2011: New developments in the family and domain prediction database. Nucleic Acids Res. 40, D306–D312.Google Scholar
  76. 76.
    Wu G., Xiao M., Yang C., et al. 2011. U2 snRNA is inducibly pseudouridylated at novel sites by Pus7p and snR81 RNP. EMBO J. 30, 79–89.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Courtes F.C., Gu C., Wong N.S.C., et al. 2014. 28S rRNA is inducibly pseudouridylated by the mTOR pathway translational control in CHO cell cultures. J. Biotechnol. 174, 16–21.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Bakin A., Ofengand J. 1993. Four newly located pseudouridylate residues in Escherichia coli 23S ribosomal RNA are all at the peptidyltransferase center: Analysis by the application of a new sequencing technique. Biochemistry. 32, 9754–9762.PubMedCrossRefGoogle Scholar
  79. 79.
    Karikó K., Muramatsu H., Welsh F.A., et al. 2008. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Karijolich J., Yu Y.-T. 2011. Converting nonsense codons into sense codons by targeted pseudouridylation. Nature. 474, 395–398.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Nishikura K. 2010. Functions and regulation of RNA editing by ADAR deaminases. Annu. Rev. Biochem. 79, 321–349.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Rueter S.M., Dawson T.R., Emeson R.B. 1999. Regulation of alternative splicing by RNA editing. Nature. 399, 75–80.PubMedCrossRefGoogle Scholar
  83. 83.
    Bass B.L. 2002. RNA editing by adenosine deaminases that act on RNA. Annu. Rev. Biochem. 71, 817.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Jepson J.E.C., Reenan R.A. 2008. RNA editing in regulating gene expression in the brain. Biochim. Biophys. Acta—Gene Regul. Mech. 1779, 459–470.CrossRefGoogle Scholar
  85. 85.
    Kim U., Wang Y., Sanford T., et al. 1994. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc. Natl. Acad. Sci. U. S. A. 91, 11457–11461.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Lai F., Chen C.-X., Carter K.C., et al. 1997. Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases. Mol. Cell. Biol. 17, 2413–2424.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Chen C.X., Cho D.S., Wang Q., et al. 2000. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both singleand doublestranded RNA binding domains. RNA. 6, 755–767.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Slavov D., Crnogorac-Jurevi T., Clark M., et al. 2000. Comparative analysis of the DRADA A-to-I RNA editing gene from mammals, pufferfish and zebrafish. Gene. 250, 53–60.PubMedCrossRefGoogle Scholar
  89. 89.
    Cho D.-S.C., Yang W., Lee J.T., et al. 2003. Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. J. Biol. Chem. 278, 17093–17102.PubMedCrossRefGoogle Scholar
  90. 90.
    Slotkin W., Nishikura K. 2013. Adenosine-to-inosine RNA editing and human disease. Genome Med. 5, 105.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Nigita G., Veneziano D., Ferro A. 2015. A-to-I RNA editing: Current knowledge sources and computational approaches with special emphasis on non-coding RNA molecules. Front. Bioeng. Biotechnol. 3, 37.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Li J.B., Levanon E.Y., Yoon J.-K., et al. 2009. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing. Science. 324, 1210–1213.PubMedCrossRefGoogle Scholar
  93. 93.
    Sakurai M., Yano T., Kawabata H., et al. 2010. Inosine cyanoethylation identifies A-to-I RNA editing sites in the human transcriptome. Nat. Chem. Biol. 6, 733–740.PubMedCrossRefGoogle Scholar
  94. 94.
    Sakurai M., Ueda H., Yano T., et al. 2014. A biochemical landscape of A-to-I RNA editing in the human brain transcriptome. Genome Res. 24, 522–534.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Lomeli H., Mosbacher J., Melcher T., et al. 1994. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science. 266, 1709–1713.PubMedCrossRefGoogle Scholar
  96. 96.
    Verdoorn T.A., Burnashev N., Monyer H., et al. 1991. Structural determinants of ion flow through recombinant glutamate receptor channels. Science. 252, 1715–1718.PubMedCrossRefGoogle Scholar
  97. 97.
    Hume R.I., Dingledine R., Heinemann S.F. 1991. Identification of a site in glutamate receptor subunits that controls calcium permeability. Science. 253, 1028–1031.PubMedCrossRefGoogle Scholar
  98. 98.
    Higuchi M., Maas S., Single F.N., et al. 2000. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature. 406, 78–81.PubMedCrossRefGoogle Scholar
  99. 99.
    Kwak S., Kawahara Y. 2005. Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis. J. Mol. Med. 83, 110–120.PubMedCrossRefGoogle Scholar
  100. 100.
    Maas S., Patt S., Schrey M., et al. 2001. Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc. Natl. Acad. Sci. U. S. A. 98, 14687–14692.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Takuma H., Kwak S., Yoshizawa T., et al. 1999. Reduction of GluR2 RNA editing, a molecular change that increases calcium influx through AMPA receptors, selective in the spinal ventral gray of patients with amyotrophic lateral sclerosis. Ann. Neurol. 46, 806–815.PubMedCrossRefGoogle Scholar
  102. 102.
    Kawahara Y., Ito K., Sun H., et al. 2004. Glutamate receptors: RNA editing and death of motor neurons. Nature. 427, 801.PubMedCrossRefGoogle Scholar
  103. 103.
    Peng P.L., Zhong X., Tu W., et al. 2006. ADAR2dependent RNA editing of AMPA receptor subunit GluR2 determines vulnerability of neurons in forebrain ischemia. Neuron. 49, 719–733.PubMedCrossRefGoogle Scholar
  104. 104.
    Burns C.M., Chu H., Rueter S.M., et al. 1997. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature. 387, 303–308.PubMedCrossRefGoogle Scholar
  105. 105.
    Marion S., Weiner D.M., Caron M.G. 2004. RNA editing induces variation in desensitization and trafficking of 5-hydroxytryptamine 2c receptor isoforms. J. Biol. Chem. 279, 2945–2954.PubMedCrossRefGoogle Scholar
  106. 106.
    Kawahara Y., Grimberg A., Teegarden S., et al. 2008. Dysregulated editing of serotonin 2C receptor mRNAs results in energy dissipation and loss of fat mass. J. Neurosci. 28, 12834–12844.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Iwamoto K., Bundo M., Kato T. 2009. Serotonin receptor 2C and mental disorders: Genetic, expression, and RNA editing studies. RNA Biol. 6, 248–253.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2015

Authors and Affiliations

  • I. G. Laptev
    • 1
  • A. Ya. Golovina
    • 2
  • P. V. Sergiev
    • 1
    • 2
  • O. A. Dontsova
    • 1
    • 2
  1. 1.Department of ChemistryMoscow State UniversityMoscowRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyMoscow State UniversityMoscowRussia

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