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RNA editing in eukaryotic genome expression

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Abstract

The present review surveys the available data on the involvement of adenine deamination in RNA molecules in the formation of structurally and functionally diverse RNA and protein subforms in eukaryotic cells. Deamination of adenine by adenosine deaminases that act on RNA (ADARs) leads to the conversion of adenine into inosine (A-I editing) recognized by the splicing and translation systems as guanine. This may modify splicing sites in pre-mRNA and codons in translated regions of mRNA and also affect the RNA secondary structure. Apart from mRNA, editing also involves microRNAs whose regulatory functions in multicellular animals are associated with the inhibition of transcription of target genes or with the degradation of certain RNA transcripts. ADARs can inhibit the production of mature microRNAs or modify microRNAs so that their specificity to target genes is altered. Adenosine deaminases editing adenines in transport RNAs (ADATs) convert adenine into inosine in tRNAs of all eukaryotes; as a result, the diversity of tRNA forms in the cell increases.

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References

  1. Maas, S., Rich, A., and Nishikura, K., A-to-I RNA Editing: Recent News and Residual Mysteries, J. Biol. Chem., 2003, vol. 278, pp. 1391–1394.

    Article  CAS  PubMed  Google Scholar 

  2. Patterson, J.B. and Samuel, C.E., Expression and Regulation by Interferon of a Double-Stranded-RNASpecific Adenosine Deaminase from Human Cells: Evidence for Two Forms of the Deaminase, Mol. Cell. Biol., 1995, vol. 15, pp. 5376–5388.

    CAS  PubMed  Google Scholar 

  3. Brusa, R., Zimmermann, F., Koh, D.S., et al., EarlyOnset Epilepsy and Postnatal Lethality Associated with an Editing-Deficient GluR-B Allele in Mice, Science, 1995, vol. 270, p. 1677–1680.

    Article  CAS  PubMed  Google Scholar 

  4. Gurevich, I., Tamir, H., Arango, V., et al., Altered Editing of Serotonin 2C Receptor pre-mRNA in the Prefrontal Cortex of Depressed Suicide Victims, Neuron, 2002, vol. 34, pp. 349–356.

    Article  CAS  PubMed  Google Scholar 

  5. Kawahara, Y., Ito, K., Sun, H., et al., Glutamate Receptors: RNA Editing and Death of Motor Neurons, Nature, 2004, vol. 427, pp. 801–803.

    Article  CAS  PubMed  Google Scholar 

  6. Rubtsov, P.M., Alternative Promoters and RNA Processing during Eukaryotic Genome Expression, Mol. Biol. (Moscow), 2000, vol. 34, pp. 626–634.

    CAS  Google Scholar 

  7. O’hman, M., A-to-I Editing Challenger or Ally to the MicroRNA Process, Biochimie, 2007, vol. 89, pp. 1171–1176.

    Article  CAS  Google Scholar 

  8. Keegan, L.P., Leroy, A., Sproul, D., and O’Connell, M.A., Adenosine Deaminases Acting on RNA (ADAR): RNA-Editing Enzymes, Genome Biol., 2004, vol. 5, pp. 209–218.

    Article  PubMed  Google Scholar 

  9. Chilibeck, K.A., Wu, T., Liang, C., et al., FRET Analysis of in vivo Dimerization by RNA-Editing Enzymes, J. Biol. Chem., 2006, vol. 281, pp. 16530–16535.

    Article  CAS  PubMed  Google Scholar 

  10. Hallegger, M., Taschner, A., and Jantsch, M.F., RNA Aptamers Binding the Double-Stranded RNA-Binding Domain, RNA, 2006, vol. 12, pp. 1993–2004.

    Article  CAS  PubMed  Google Scholar 

  11. George, C.X., Wagner, M.V., and Samuel, C.E., Expression of Interferon-Inducible RNA Adenosine Deaminase ADAR1 during Pathogen Infection and Mouse Embryo Development Involves Tissue-Selective Promoter Utilization and Alternative Splicing, J. Biol. Chem., 2005, vol. 280, pp. 15020–15028.

    Article  CAS  PubMed  Google Scholar 

  12. Desterro, J.M., Keegan, L.P., Lafarga, M., et al., Dynamic Association of RNA-Editing Enzymes with the Nucleolus, J. Cell Sci., 2003, vol. 116, pp. 1805–1818.

    Article  CAS  PubMed  Google Scholar 

  13. Liu, Y. and Samuel, C.E., Editing of Glutamate Receptor Subunit B pre-mRNA by Splice-Site Variants of Interferon-Inducible Double-Stranded RNA-Specific Adenosine Deaminase ADAR1, J. Biol. Chem., 1999, vol. 274, pp. 5070–5077.

    Article  CAS  PubMed  Google Scholar 

  14. Hartner, J.C., Schmittwolf, C., Kispert, A., et al., Liver Disintegration in the Mouse Embryo by Deficiency in RNA Editing Enzyme ADAR1, J. Biol. Chem., 2004, vol. 279, pp. 4894–4902.

    Article  CAS  PubMed  Google Scholar 

  15. Wang, Q., Miyakoda, M., Yang, W., et al., StressInduced Apoptosis Associated with Null Mutation of ADAR1 RNA Editing Deaminase Gene, J. Biol. Chem., 2004, vol. 279, pp. 4952–4961.

    Article  CAS  PubMed  Google Scholar 

  16. Higuchi, M., Maas, S., Single, F.N., et al., Point Mutation in an AMPA Receptor Gene Rescues Lethality in Mice Deficient in the RNA-Editing Enzyme ADAR2, Nature, 2000, vol. 406, pp. 78–81.

    Article  CAS  PubMed  Google Scholar 

  17. Gerber, A., Grosjean, H., Melcher, T., and Keller, W., Tad1p, a Yeast tRNA-Specific Adenosine Deaminase, Is Related to the Mammalian pre-mRNA Editing Enzymes ADAR1 and ADAR2, EMBO J., 1998, vol. 17, pp. 4780–4789.

    Article  CAS  PubMed  Google Scholar 

  18. Gerber, A.P. and Keller, W., An Adenosine Deaminase That Generates Inosine at the Wobble Position of tRNAs, Science, 1999, vol. 286, pp. 1146–1149.

    Article  CAS  PubMed  Google Scholar 

  19. Wolf, J., Gerber, A.P., and Keller, W., tadA, an Essential tRNA-Specific Adenosine Deaminase from Escherichia coli, EMBO J., 2002, vol. 21, pp. 3841–3851.

    Article  CAS  PubMed  Google Scholar 

  20. Morse, D.P., Aruscavage, P.J., and Bass, B.L., RNA Hairpins in Noncoding Regions of Human Brain and Caenorhabditis elegans mRNA Are Edited by Adenosine Deaminases That Act on RNA, Proc. Natl. Acad. Sci. USA, 2002, vol. 99, pp. 7906–7911.

    Article  CAS  PubMed  Google Scholar 

  21. Levanon, E.Y., Eisenberg, E., Yelin, R., et al., Systematic Identification of Abundant A-to-I Editing Sites in the Human Transcriptome, Nat. Biotechnol., 2004, vol. 22, pp. 1001–1005.

    Article  CAS  PubMed  Google Scholar 

  22. Kumar, M. and Carmichael, G.C., Nuclear Antisense RNA Induces Extensive Adenosine Modifications and Nuclear Retention of Target Transcripts, Proc. Natl. Acad. Sci. USA, 1997, vol. 94, pp. 3542–3547.

    Article  CAS  PubMed  Google Scholar 

  23. Ohlson, J., Pedersen, J.S., Haussler, D., and O“hman, M., Editing Modifies the GABAA Receptor Subunit α′3, RNA, 2007, vol. 13, pp. 698–703.

    Article  CAS  PubMed  Google Scholar 

  24. Stapleton, M., Carlson, J.W., and Celniker, S.E., RNA Editing in Drosophila melanogaster: New Targets and Functional Consequences, RNA, 2006, vol. 12, pp. 1922–1932.

    Article  CAS  PubMed  Google Scholar 

  25. Xia, S., Yang, J., Su, Y., et al., Identification of New Targets of Drosophila pre-mRNA Adenosine Deaminase, Physiol. Genomics, 2005, vol. 20, pp. 195–202.

    Article  CAS  PubMed  Google Scholar 

  26. Levanon, E.Y., Hallegger, M., Kinar, Y., et al., Evolutionarily Conserved Human Targets of Adenosine to Inosine RNA Editing, Nucleic Acids Res., 2005, vol. 33, pp. 1162–1168.

    Article  CAS  PubMed  Google Scholar 

  27. Hoopengardner, B., Bhalla, T., Staber, C., and Reenan, R., Nervous System Targets of RNA Editing Identified by Comparative Genomics, Science, 2003, vol. 301, pp. 832–836.

    Article  CAS  PubMed  Google Scholar 

  28. Seeburg, P.H., A-to-I Editing: New and Old Sites Functions and Speculations, Neuron, 2002, vol. 35, pp. 17–20.

    Article  CAS  PubMed  Google Scholar 

  29. Jepson, J.E.C. and Reenan, R.A., RNA Editing in Regulating Gene Expression in the Brain, Biochimica et Biophysica Acta, 2008.

  30. Higuchi, M., Single, F.N., Köhler, M., et al., RNA Editing of AMPA Receptor Subunit GluR-B: A Basepaired Intron-Exon Structure Determines Position and Efficiency, Cell, 1993, vol. 75, pp. 1361–1370.

    Article  CAS  PubMed  Google Scholar 

  31. Sommer, B., Kohler, M., Sprengel, R., and Seeburg, P.H., RNA Editing in Brain Controls a Determinant of Ion Flow in Glutamate-Gated Channels, Cell, 1991, vol. 67, pp. 11–19.

    Article  CAS  PubMed  Google Scholar 

  32. Verdoorn, T.A., Burnashev, N., Monyer, H., et al., Structural Determinants of Ion Flow through Recombinant Glutamate Receptor Channels, Science, 1991, vol. 252, pp. 1715–1718.

    Article  CAS  PubMed  Google Scholar 

  33. Greger, I.H., Khatri, L., and Ziff, E.B., RNA Editing at arg607 Controls AMPA Receptor Exit from the Endoplasmic Reticulum, Neuron, 2002, vol. 34, pp. 759–772.

    Article  CAS  PubMed  Google Scholar 

  34. Penn, A.C., Williams, S.R., and Greger, I.H., Gating Motions Underlie AMPA Receptor Secretion from the Endoplasmic Reticulum, EMBO J., 2008, vol. 27, pp. 3056–3068.

    Article  CAS  PubMed  Google Scholar 

  35. Greger, I.H., Khatri, L., Kong, X., and Ziff, E.B., AMPA Receptor Tetramerization Is Mediated by Q/R Editing, Neuron, 2003, vol. 40, pp. 763–774.

    Article  CAS  PubMed  Google Scholar 

  36. Greger, I.H. and Esteban, J.A., AMPA Receptor Biogenesis and Trafficking, Curr. Opinion Neurobiol., 2007, vol. 17, pp. 289–297.

    Article  CAS  Google Scholar 

  37. Grauso, M., Reenan, R.A., Culetto, E., and Sattelle, D.B., Novel Putative Nicotinic Acetylcholine Receptor Subunit Genes, Dalpha5, Dalpha6 and Dalpha7, in Drosophila melanogaster Identify a New and Highly Conserved Target of Adenosine Deaminase Acting on RNA-Mediated A-to-I Pre-mRNA Editing, Genetics, 2002, vol. 160, pp. 1519–1533.

    CAS  PubMed  Google Scholar 

  38. Hoopengardner, B., Bhalla, T., Staber, C., and Reenan, R., Nervous System Targets of RNA Editing Identified by Comparative Genomics, Science, 2003, vol. 301, pp. 832–836.

    Article  CAS  PubMed  Google Scholar 

  39. Semenov, E.P. and Pak, W.L., Diversification of Drosophila Chloride Channel Gene by Multiple Posttranscriptional mRNA Modifications, J. Neurochem., 1999, vol. 72, pp. 66–72.

    Article  CAS  PubMed  Google Scholar 

  40. Sattelle, D.B., Jones, A.K., Sattelle, B.M., et al., Edit, Cut and Paste in the Nicotinic Acetylcholine Receptor Gene Family of Drosophila melanogaster, BioEssays, 2005, vol. 27, pp. 366–376.

    Article  CAS  PubMed  Google Scholar 

  41. Jin, Y., Tian, N., Cao, J., et al., RNA Editing and Alternative Splicing of the Insect nAChR Subunit Alpha6 Transcript: Evolutionary Conservation, Divergence and Regulation, BMC Evol. Biol., 2007, vol. 7, pp. 98–110.

    Article  PubMed  CAS  Google Scholar 

  42. Rosenthal, J.J. and Bezanilla, F., Extensive Editing of mRNAs for the Squid Delayed Rectifier K+ Channel Regulates Subunit Tetramerization, Neuron, 2002, vol. 34, pp. 743–757.

    Article  CAS  PubMed  Google Scholar 

  43. Burns, C.M., Chu, H., Rueter, S.M., et al., Regulation of Serotonin-2C Receptor G Protein Coupling by RNA Editing, Nature, 1997, vol. 387, pp. 303–308.

    Article  CAS  PubMed  Google Scholar 

  44. Wang, Q., O’Brien, P.J., Chen, C.X., et al., Altered G Protein-Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin2C Receptors, Neurochem, 2000, vol. 74, pp. 1290–1300.

    Article  CAS  Google Scholar 

  45. Niswender, C.M., Herrick-Davis, K., Dilley, G.E., et al., RNA Editing of the Human Serotonin 5-HT2C Receptor: Alterations in Suicide and Implications for Serotonergic Pharmacotherapy, Neuropsychopharmacology, 2001, vol. 24, pp. 478–491.

    Article  CAS  PubMed  Google Scholar 

  46. Sodhi, M.S., Burnet, P.W., Makoff, A.J., et al., RNA Editing of the 5-HT(2C) Receptor Is Reduced in Schizophrenia, Mol. Psychiatry, 2001, vol. 6, pp. 373–379.

    Article  CAS  PubMed  Google Scholar 

  47. Nishiki, T. and Augustine, G.J., Dual Roles of the C2B Domain of Synaptotagmin I in Synchronizing Ca2+Dependent Neurotransmitter Release, J. Neurosci., 2004, vol. 24, pp. 8542–8550.

    Article  CAS  PubMed  Google Scholar 

  48. Rueter, S.M., Dawson, T.R., and Emeson, R.B., Regulation of Alternative Splicing by RNA Editing, Nature, 1999, vol. 399, pp. 75–80.

    Article  CAS  PubMed  Google Scholar 

  49. Levanon, E.Y., Eisenberg, E., Yelin, R., et al., Systematic Identification of Abundant A-to-I Editing Sites in the Human Transcriptome, Nat. Biotechnol., 2004, vol. 22, pp. 1001–1005.

    Article  CAS  PubMed  Google Scholar 

  50. Kim, D.D., Kim, T.T., Walsh, T., et al., Widespread RNA Editing of Embedded Alu Elements in the Human Transcriptome, Genome Res., 2004, vol. 14, pp. 1719–1725.

    Article  CAS  PubMed  Google Scholar 

  51. Athanasiadis, A., Rich, A., and Maas, S., Widespread A-to-I RNA Editing of Alu-Containing mRNAs in the Human Transcriptome, PLoS Biol., 2004, vol. 2, pp. 2144–2158.

    Article  CAS  Google Scholar 

  52. Blow, M., Futreal, P.A., Wooster, R., and Stratton, M.R., A Survey of RNA Editing in Human Brain, Genome Res., 2004, vol. 14, pp. 2379–2387.

    Article  CAS  PubMed  Google Scholar 

  53. Lee, Y., Jeon, K., Lee, J.T., et al., MicroRNA Maturation: Stepwise Processing and Subcellular Localization, EMBO J., 2002, vol. 21, pp. 4663–4670.

    Article  CAS  PubMed  Google Scholar 

  54. Lund, E., Guttinger, S., Calado, A., et al., Nuclear Export of MicroRNA Precursors, Science, 2004, vol. 303, pp. 95–98.

    Article  CAS  PubMed  Google Scholar 

  55. Hutvagner, G., McLachlan, J., Pasquinelli, A.E., et al., A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the Let-7 Small Temporal RNA, Science, 2001, vol. 293, pp. 834–838.

    Article  CAS  PubMed  Google Scholar 

  56. Bartel, D.P., MicroRNAs: Genomics, Biogenesis, Mechanism, and Function, Cell, 2004, vol. 116, pp. 281–297.

    Article  CAS  PubMed  Google Scholar 

  57. Bass, B.L., Double-Stranded RNA as a Template for Gene Silencing, Cell, 2000, vol. 101, pp. 235–238.

    Article  CAS  PubMed  Google Scholar 

  58. Tonkin, L.A., Saccomanno, L., Morse, D.P., et al., RNA Editing by ADAR Is Important for Normal Behavior in Caenorhabditis elegans, EMBO J., 2002, vol. 21, pp. 6025–6035.

    Article  CAS  PubMed  Google Scholar 

  59. Tonkin, L.A. and Bass, B.L., Mutations in RNAi Rescue Aberrant Chemotaxis of ADAR Mutants, Science, 2003, vol. 302, p. 1725.

  60. Liang, H. and Landweber, L.F., Hypothesis: RNA Editing of MicroRNA Target Sites in Humans?, RNA, 2007, vol. 13, pp. 463–467.

    Article  CAS  PubMed  Google Scholar 

  61. Yang, W., Chendrimada, T.P., Wang, Q., et al., Modulation of MicroRNA Processing and Expression through RNA Editing by ADAR Deaminases, Nat. Struct. Mol. Biol., 2006, vol. 13, pp. 13–21.

    Article  CAS  PubMed  Google Scholar 

  62. Kawahara, Y., Zinshteyn, B., Sethupathy, P., et al., Redirection of Silencing Targets by Adenosine-toInosine Editing of miRNAs, Science, 2007, vol. 315, pp. 1137–1140.

    Article  CAS  PubMed  Google Scholar 

  63. Smith, H.C. and Sowden, M.P., Base-Modification mRNA Editing through Deamination-the Good, the Bad and the Unregulated, Trends Gene, 1996, vol. 12, pp. 418–424.

    Article  CAS  Google Scholar 

  64. Ochsenreiter, T., Cipriano, M., and Hajduk, S.L., Alternative mRNA Editing in Trypanosomes Is Extensive and May Contribute to Mitochondrial Protein Diversity, PLoS, 2008, vol. 3, pp. 1–8.

    Google Scholar 

  65. Hanrahan, C.J., Palladino, M.J., Ganetzky, B., and Reenan, R.A., RNA Editing of the Drosophila Para Na+ Channel Transcript: Evolutionary Conservation and Developmental Regulation, Genetics, 2000, vol. 155, pp. 1149–1160.

    CAS  PubMed  Google Scholar 

  66. Reenan, R.A., Hanrahan, C.J., and Barry, G., The mle(napts) RNA Helicase Mutation in Drosophila Results in a Splicing Catastrophe of the Para Na+ Channel Transcript in a Region of RNA Editing, Neuron, 2000, vol. 25, pp. 139–149.

    Article  CAS  PubMed  Google Scholar 

  67. Pankratova, E.V., Alternative Promoters in Expression of Genetic Information, Mol. Biol. (Moscow), 2008, vol. 42, pp. 1–12.

    Google Scholar 

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  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    E. V. Pankratova & A. G. Stepchenko

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Original Russian Text © E.V. Pankratova, A.G. Stepchenko, 2010, published in Genetika, 2010, Vol. 46, No. 1, pp. 5–13.

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Pankratova, E.V., Stepchenko, A.G. RNA editing in eukaryotic genome expression. Russ J Genet 46, 1–8 (2010). https://doi.org/10.1134/S1022795410010011

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