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RNA Editing pp 51–84Cite as

RNA Editing by Adenosine Deaminases that Act on RNA (ADARs)

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Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 20))

Abstract

Adenosine deaminases that act on RNA (ADARs) give rise to the most abundant form of RNA editing found in Metazoa. ADAR proteins convert adenosines to inosines within structured and double-stranded RNAs. Since inosines are interpreted as guanosines by several cellular machineries, the consequences of editing can be widespread. In messenger RNA, alterations of codons, changes in splice patterns, and influences on RNA stability have been observed as a result of RNA editing. Moreover, A to I editing has been shown to interconnect with the RNA interference machinery. In this chapter, an overview on ADAR enzymes, their molecular architecture, occurrence, and substrate specificity is given. Consequences of editing, studies in model organisms, and implications for other double-stranded RNA-dependent processes are discussed.

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References

  • Agrawal R, Stormo GD (2005) Editing efficiency of a Drosophila gene correlates with a distant splice site selection. RNA 11:563–566.

    PubMed  CAS  Google Scholar 

  • Allan BW, Reich NO (1996) Targeted base stacking disruption by the EcoRI DNA methyltransferase. Biochemistry 35:14757–14762.

    PubMed  CAS  Google Scholar 

  • Athanasiadis A, Rich A, Maas S (2004) Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biol 2:e391.

    PubMed  Google Scholar 

  • Bass BL (2002) RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem 71:817–846.

    PubMed  CAS  Google Scholar 

  • Bass BL, Weintraub H (1988) An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55:1089–1098.

    PubMed  CAS  Google Scholar 

  • Bass BL, Nishikura K, Keller W, Seeburg PH, Emeson RB, O’Connell MA, Samuel CE, Herbert A (1997) A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3:947–949.

    PubMed  CAS  Google Scholar 

  • Beghini A, Ripamonti CB, Peterlongo P, Roversi G, Cairoli R, Morra E, Larizza L (2000) RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. Hum Mol Genet 9:2297–2304.

    PubMed  CAS  Google Scholar 

  • Bhalla T, Rosenthal JJ, Holmgren M, Reenan R (2004) Control of human potassium channel inactivation by editing of a small mRNA hairpin. Nat Struct Mol Biol 11:950–956.

    PubMed  CAS  Google Scholar 

  • Blow M, Futreal PA, Wooster R, Stratton MR (2004) A survey of RNA editing in human brain. Genome Res 14:2379–2387.

    PubMed  CAS  Google Scholar 

  • Blow MJ, Grocock RJ, van Dongen S, Enright AJ, Dicks E, Futreal PA, Wooster R, Stratton MR (2006) RNA editing of human microRNAs. Genome Biol 7:R27.

    PubMed  Google Scholar 

  • Bratt E, Öhman M (2003) Coordination of editing and splicing of glutamate receptor pre-mRNA. RNA 9:309–318.

    PubMed  CAS  Google Scholar 

  • Brusa R, Zimmermann F, Koh DS, Feldmeyer D, Gass P, Seeburg PH, Sprengel R (1995) Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Science 270:1677–1680.

    PubMed  CAS  Google Scholar 

  • Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387:303–308.

    PubMed  CAS  Google Scholar 

  • Casey JL, Gerin JL (1995) Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA. J Virol 69:7593–7600.

    PubMed  CAS  Google Scholar 

  • Cattaneo R (1994) Biased (A–>I) hypermutation of animal RNA virus genomes. Curr Opin Genet Dev 4:895–900.

    PubMed  CAS  Google Scholar 

  • Caudy AA, Ketting RF, Hammond SM, Denli AM, Bathoorn AM, Tops BB, Silva JM, Myers MM, Hannon GJ, Plasterk RH (2003) A micrococcal nuclease homologue in RNAi effector complexes. Nature 425:411–414.

    PubMed  CAS  Google Scholar 

  • Chang FL, Chen PJ, Tu SJ, Wang CJ, Chen DS (1991) The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci USA 88:8490–8494.

    PubMed  CAS  Google Scholar 

  • Chen CX, Cho DS, Wang Q, Lai F, Carter KC, Nishikura K (2000) A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA 6:755–767.

    PubMed  CAS  Google Scholar 

  • Cho DS, Yang W, Lee JT, Shiekhattar R, Murray JM, Nishikura K (2003) Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. J Biol Chem 278:17093–17102.

    PubMed  CAS  Google Scholar 

  • Clutterbuck DR, Leroy A, O’Connell MA, Semple CA (2005) A bioinformatic screen for novel A-I RNA editing sites reveals recoding editing in BC10. Bioinformatics 21:2590–2595.

    PubMed  CAS  Google Scholar 

  • Dawson TR, Sansam CL, Emeson RB (2004) Structure and sequence determinants required for the RNA editing of ADAR2 substrates. J Biol Chem 279:4941–4951.

    PubMed  CAS  Google Scholar 

  • Desterro JM, Keegan LP, Lafarga M, Berciano MT, O’Connell M, Carmo-Fonseca M (2003) Dynamic association of RNA-editing enzymes with the nucleolus. J Cell Sci 116:1805–1818.

    PubMed  CAS  Google Scholar 

  • Doyle M, Jantsch MF (2003) Distinct in vivo roles for double-stranded RNA-binding domains of the Xenopus RNA-editing enzyme ADAR1 in chromosomal targeting. J Cell Biol 161:309–319.

    PubMed  CAS  Google Scholar 

  • Eckmann CR, Jantsch MF (1999) The RNA-editing enzyme ADAR1 is localized to the nascent ribonucleoprotein matrix on Xenopus lampbrush chromosomes but specifically associates with an atypical loop. J Cell Biol 144:603–615.

    PubMed  CAS  Google Scholar 

  • Eckmann CR, Neunteufl A, Pfaffstetter L, Jantsch MF (2001) The human but not the Xenopus RNA-editing enzyme ADAR1 has an atypical nuclear localization signal and displays the characteristics of a shuttling protein. Mol Biol Cell 12:1911–1924.

    PubMed  CAS  Google Scholar 

  • Eisenberg E, Nemzer S, Kinar Y, Sorek R, Rechavi G, Levanon EY (2005) Is abundant A-to-I RNA editing primate-specific? Trends Genet 21:77–81.

    PubMed  CAS  Google Scholar 

  • Fernandez HR, Kavi HH, Xie W, Birchler JA (2005) Heterochromatin: on the ADAR radar? Curr Biol 15:R132–134.

    PubMed  CAS  Google Scholar 

  • Gallo A, Keegan LP, Ring GM, O’Connell MA (2003) An ADAR that edits transcripts encoding ion channel subunits functions as a dimer. EMBO J 22:3421–3430.

    PubMed  CAS  Google Scholar 

  • Geiger JR, Melcher T, Koh DS, Sakmann B, Seeburg PH, Jonas P, Monyer H (1995) Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron 15:193–204.

    PubMed  CAS  Google Scholar 

  • George CX, Samuel CE (1999) Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible. Proc Natl Acad Sci USA 96:4621–4626.

    PubMed  CAS  Google Scholar 

  • Gerber A, Grosjean H, Melcher T, Keller W (1998) Tad1p, a yeast tRNA-specific adenosine deaminase, is related to the mammalian pre-mRNA editing enzymes ADAR1 and ADAR2. EMBO J 17:4780–4789.

    PubMed  CAS  Google Scholar 

  • Grabowski PJ, Black DL (2001) Alternative RNA splicing in the nervous system. Prog Neurobiol 65:289–308.

    PubMed  CAS  Google Scholar 

  • Greger IH, Khatri L, Ziff EB (2002) RNA editing at arg607 controls AMPA receptor exit from the endoplasmic reticulum. Neuron 34:759–772.

    PubMed  CAS  Google Scholar 

  • Greger IH, Khatri L, Kong X, Ziff EB (2003) AMPA receptor tetramerization is mediated by Q/R editing. Neuron 40:763–774.

    PubMed  CAS  Google Scholar 

  • Gu R, Zhang Z, Carmichael GG (2007) How a small DNA virus uses dsRNA but not RNAi to regulate its life cycle. Cold Spring Harbor Symp Quant Biol LXXI:1–7.

    Google Scholar 

  • Gurevich I, Englander MT, Adlersberg M, Siegal NB, Schmauss C (2002) Modulation of serotonin 2C receptor editing by sustained changes in serotonergic neurotransmission. J Neurosci 22:10529–10532.

    PubMed  CAS  Google Scholar 

  • Hanrahan CJ, Palladino MJ, Ganetzky B, Reenan RA (2000) RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary conservation and developmental regulation. Genetics 155:1149–1160.

    PubMed  CAS  Google Scholar 

  • Hartner JC, Schmittwolf C, Kispert A, Muller AM, Higuchi M, Seeburg PH (2004) Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. J Biol Chem 279:4894–4902.

    PubMed  CAS  Google Scholar 

  • Herbert A, Rich A (2001) The role of binding domains for dsRNA and Z-DNA in the in vivo editing of minimal substrates by ADAR1. Proc Natl Acad Sci USA 98:12132–12137.

    PubMed  CAS  Google Scholar 

  • Herbert A, Alfken J, Kim YG, Mian IS, Nishikura K, Rich A (1997) A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase. Proc Natl Acad Sci USA 94:8421–8426.

    PubMed  CAS  Google Scholar 

  • Herbert A, Schade M, Lowenhaupt K, Alfken J, Schwartz T, Shlyakhtenko LS, Lyubchenko YL, Rich A (1998) The Zalpha domain from human ADAR1 binds to the Z-DNA conformer of many different sequences. Nucleic Acids Res 26:3486–3493.

    PubMed  CAS  Google Scholar 

  • Higuchi M, Maas S, Single FN, Hartner J, Rozov A, Burnashev N, Feldmeyer D, Sprengel R, Seeburg PH (2000) Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406:78–81.

    PubMed  CAS  Google Scholar 

  • Hoopengardner B, Bhalla T, Staber C, Reenan R (2003) Nervous system targets of RNA editing identified by comparative genomics. Science 301:832–836.

    PubMed  CAS  Google Scholar 

  • Hough RF, Bass BL (1997) Analysis of Xenopus dsRNA adenosine deaminase cDNAs reveals similarities to DNA methyltransferases. RNA 3:356–370.

    PubMed  CAS  Google Scholar 

  • Huertas D, Cortes A, Casanova J, Azorin F (2004) Drosophila DDP1, a multi-KH-domain protein, contributes to centromeric silencing and chromosome segregation. Curr Biol 14:1611–1620.

    PubMed  CAS  Google Scholar 

  • Iwamoto K, Nakatani N, Bundo M, Yoshikawa T, Kato T (2005) Altered RNA editing of serotonin 2C receptor in a rat model of depression. Neurosci Res 53:69–76.

    PubMed  CAS  Google Scholar 

  • Jayan GC, Casey JL (2002) Inhibition of hepatitis delta virus RNA editing by short inhibitory RNA-mediated knockdown of ADAR1 but not ADAR2 expression. J Virol 76:12399–12404.

    PubMed  CAS  Google Scholar 

  • Källman AM, Sahlin M, Öhman M (2003) ADAR2 A–>I editing: site selectivity and editing efficiency are separate events. Nucleic Acids Res 31:4874–4881.

    PubMed  Google Scholar 

  • Kawahara Y, Ito K, Sun H, Aizawa H, Kanazawa I, Kwak S (2004) Glutamate receptors: RNA editing and death of motor neurons. Nature 427:801.

    PubMed  CAS  Google Scholar 

  • Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K (2007a) Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 315:1137–1140.

    PubMed  CAS  Google Scholar 

  • Kawahara Y, Zinshteyn B, Chendrimada TP, Shiekhattar R, Nishikura K (2007b) RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep 8:763–769.

    PubMed  CAS  Google Scholar 

  • Keegan LP, Brindle J, Gallo A, Leroy A, Reenan RA, O’Connell MA (2005) Tuning of RNA editing by ADAR is required in Drosophila. EMBO J 24:2183–2193.

    PubMed  CAS  Google Scholar 

  • Kim U, Wang Y, Sanford T, Zeng Y, Nishikura K (1994) Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci USA 91:11457–11461.

    PubMed  CAS  Google Scholar 

  • Kim YG, Lowenhaupt K, Maas S, Herbert A, Schwartz T, Rich A (2000) The Zab domain of the human RNA editing enzyme ADAR1 recognizes Z-DNA when surrounded by B-DNA. J Biol Chem 275:26828–26833.

    PubMed  CAS  Google Scholar 

  • Kim DD, Kim TT, Walsh T, Kobayashi Y, Matise TC, Buyske S, Gabriel A (2004) Widespread RNA editing of embedded Alu elements in the human transcriptome. Genome Res 14:1719–1725.

    PubMed  CAS  Google Scholar 

  • Klaue Y, Källman AM, Bonin M, Nellen W, Öhman M (2003) Biochemical analysis and scanning force microscopy reveal productive and nonproductive ADAR2 binding to RNA substrates. RNA 9:839–846.

    PubMed  CAS  Google Scholar 

  • Knight SW, Bass BL (2002) The role of RNA editing by ADARs in RNAi. Mol Cell 10:809–817.

    PubMed  CAS  Google Scholar 

  • Kornblihtt AR, de la Mata M, Fededa JP, Munoz MJ, Nogues G (2004) Multiple links between transcription and splicing. RNA 10:1489–1498.

    PubMed  CAS  Google Scholar 

  • Kumar M, Carmichael GG (1997) Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. Proc Natl Acad Sci USA 94:3542–3547.

    PubMed  CAS  Google Scholar 

  • Kuo MY, Chao M, Taylor J (1989) Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol 63:1945–1950.

    PubMed  CAS  Google Scholar 

  • Laurencikiene J, Källman AM, Fong N, Bentley DL, Öhman M (2006) RNA editing and alternative splicing: the importance of co-transcriptional coordination. EMBO Rep 7:303–307.

    PubMed  CAS  Google Scholar 

  • Lehmann KA, Bass BL (1999) The importance of internal loops within RNA substrates of ADAR1. J Mol Biol 291:1–13.

    PubMed  CAS  Google Scholar 

  • Lehmann KA, Bass BL (2000) Double-stranded RNA adenosine deaminases ADAR1 and ADAR2 have overlapping specificities. Biochemistry 39:12875–12884.

    PubMed  CAS  Google Scholar 

  • Lejeune F, Maquat LE (2005) Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Curr Opin Cell Biol 17:309–315.

    PubMed  CAS  Google Scholar 

  • Levanon EY, Eisenberg E, Yelin R, Nemzer S, Hallegger M, Shemesh R, Fligelman ZY, Shoshan A, Pollock SR, Sztybel D, Olshansky M, Rechavi G, Jantsch MF (2004) Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat Biotechnol 22:1001–1005.

    PubMed  CAS  Google Scholar 

  • Levanon EY, Hallegger M, Kinar Y, Shemesh R, Djinovic-Carugo K, Rechavi G, Jantsch MF, Eisenberg E (2005) Evolutionarily conserved human targets of adenosine to inosine RNA editing. Nucleic Acids Res 33:1162–1168.

    PubMed  CAS  Google Scholar 

  • Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773.

    PubMed  CAS  Google Scholar 

  • Liu Y, George CX, Patterson JB, Samuel CE (1997) Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase. J Biol Chem 272:4419–4428.

    PubMed  CAS  Google Scholar 

  • Lomeli H, Mosbacher J, Melcher T, Hoger T, Geiger JR, Kuner T, Monyer H, Higuchi M, Bach A, Seeburg PH (1994) Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science 266:1709–1713.

    PubMed  CAS  Google Scholar 

  • Luciano DJ, Mirsky H, Vendetti NJ, Maas S (2004) RNA editing of a miRNA precursor. RNA 10:1174–1177.

    PubMed  CAS  Google Scholar 

  • Luo GX, Chao M, Hsieh SY, Sureau C, Nishikura K, Taylor J (1990) A specific base transition occurs on replicating hepatitis delta virus RNA. J Virol 64:1021–1027.

    PubMed  CAS  Google Scholar 

  • Maas S, Melcher T, Herb A, Seeburg PH, Keller W, Krause S, Higuchi M, O’Connell MA (1996) Structural requirements for RNA editing in glutamate receptor pre-mRNAs by recombinant double-stranded RNA adenosine deaminase. J Biol Chem 271:12221–12226.

    PubMed  CAS  Google Scholar 

  • Maas S, Patt S, Schrey M, Rich A (2001) Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc Natl Acad Sci USA 98:14687–14692.

    PubMed  CAS  Google Scholar 

  • Macbeth MR, Schubert HL, Vandemark AP, Lingam AT, Hill CP, Bass BL (2005) Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science 309:1534–1539.

    PubMed  CAS  Google Scholar 

  • Melcher T, Maas S, Herb A, Sprengel R, Higuchi M, Seeburg PH (1996a) RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J Biol Chem 271:31795–31798.

    PubMed  CAS  Google Scholar 

  • Melcher T, Maas S, Herb A, Sprengel R, Seeburg PH, Higuchi M (1996b) A mammalian RNA editing enzyme. Nature 379:460–464.

    PubMed  CAS  Google Scholar 

  • Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC (2004) Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat Genet 36:1073–1078.

    PubMed  CAS  Google Scholar 

  • Morse DP, Bass BL (1999) Long RNA hairpins that contain inosine are present in Caenorhabditis elegans poly(A)+ RNA. Proc Natl Acad Sci USA 96:6048–6053.

    PubMed  CAS  Google Scholar 

  • Morse DP, Aruscavage PJ, Bass BL (2002) 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 99:7906–7911.

    PubMed  CAS  Google Scholar 

  • Mortillaro MJ, Blencowe BJ, Wei X, Nakayasu H, Du L, Warren SL, Sharp PA, Berezney R (1996) A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix. Proc Natl Acad Sci USA 93:8253–8257.

    PubMed  CAS  Google Scholar 

  • Neugebauer KM, Roth MB (1997) Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription. Genes Dev 11:1148–1159.

    PubMed  CAS  Google Scholar 

  • Nishikura K (2004) Editing the message from A to I. Nat Biotechnol 22:962–963.

    PubMed  CAS  Google Scholar 

  • Niswender CM, Copeland SC, Herrick-Davis K, Emeson RB, Sanders-Bush E (1999) RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J Biol Chem 274:9472–9478.

    PubMed  CAS  Google Scholar 

  • O’Connell MA, Krause S, Higuchi M, Hsuan JJ, Totty NF, Jenny A, Keller W (1995) Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol Cell Biol 15:1389–1397.

    PubMed  Google Scholar 

  • Ohlson J, Pedersen JS, Haussler D, Öhman M (2007) Editing modifies the GABA(A) receptor subunit alpha3. RNA 13:698–703.

    PubMed  CAS  Google Scholar 

  • Öhman M, Källman AM, Bass BL (2000) In vitro analysis of the binding of ADAR2 to the pre-mRNA encoding the GluR-B R/G site. RNA 6:687–697.

    PubMed  Google Scholar 

  • Palladino MJ, Keegan LP, O’Connell MA, Reenan RA (2000a) A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102:437–449.

    PubMed  CAS  Google Scholar 

  • Palladino MJ, Keegan LP, O’Connell MA, Reenan RA (2000b) dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing [In Process Citation]. RNA 6:1004–1018.

    PubMed  CAS  Google Scholar 

  • Patterson JB, Samuel CE (1995) Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol Cell Biol 15:5376–5388.

    PubMed  CAS  Google Scholar 

  • Patton DE, Silva T, Bezanilla F (1997) RNA editing generates a diverse array of transcripts encoding squid Kv2 K+ channels with altered functional properties. Neuron 19:711–722.

    PubMed  CAS  Google Scholar 

  • Pinto Desterro JM, Keegan LP, Jaffray E, Hay RT, O’Connell MA, Carmo-Fonseca M (2005) SUMO-1 modification alters ADAR1 editing activity. Mol Biol Cell (in press).

    Google Scholar 

  • Polson AG, Bass BL (1994) Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase. EMBO J 13:5701–5711.

    PubMed  CAS  Google Scholar 

  • Poulsen H, Nilsson J, Damgaard CK, Egebjerg J, Kjems J (2001) CRM1 mediates the export of ADAR1 through a nuclear export signal within the Z-DNA binding domain. Mol Cell Biol 21:7862–7871.

    PubMed  CAS  Google Scholar 

  • Prasanth KV, Prasanth SG, Xuan Z, Hearn S, Freier SM, Bennett CF, Zhang MQ, Spector DL (2005) Regulating gene expression through RNA nuclear retention. Cell 123:249–263.

    PubMed  CAS  Google Scholar 

  • Ramos A, Grunert S, Adams J, Micklem DR, Proctor MR, Freund S, Bycroft M, St Johnston D, Varani G (2000) RNA recognition by a Staufen double-stranded RNA-binding domain. EMBO J 19:997–1009.

    PubMed  CAS  Google Scholar 

  • Reenan RA (2005) Molecular determinants and guided evolution of species-specific RNA editing. Nature 434:409–413.

    PubMed  CAS  Google Scholar 

  • Rosenthal JJ, Bezanilla F (2002) Extensive editing of mRNAs for the squid delayed rectifier K+ channel regulates subunit tetramerization. Neuron 34:743–757.

    PubMed  CAS  Google Scholar 

  • Rueter SM, Dawson TR, Emeson RB (1999) Regulation of alternative splicing by RNA editing. Nature 399:75–80.

    PubMed  CAS  Google Scholar 

  • Ryman K, Fong N, Bratt E, Bentley DL, Öhman M (2007) The C-terminal domain of RNA pol II helps ensure that editing precedes splicing of the GluR-B transcript. RNA 35:3723–3732.

    Google Scholar 

  • Ryter JM, Schultz SC (1998) Molecular basis of double-stranded RNA-protein interactions: structure of a dsRNA-binding domain complexed with dsRNA. EMBO J 17:7505–7513.

    PubMed  CAS  Google Scholar 

  • Sallacz NB, Jantsch MF (2005) Chromosomal storage of the RNA-editing enzyme ADAR1 in Xenopus oocytes. Mol Biol Cell 16:3377–3386.

    PubMed  CAS  Google Scholar 

  • Sansam CL, Wells KS, Emeson RB (2003) Modulation of RNA editing by functional nucleolar sequestration of ADAR2. Proc Natl Acad Sci USA 100:14018–14023.

    PubMed  CAS  Google Scholar 

  • Scadden AD (2005) The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage. Nat Struct Mol Biol 12:489–496.

    PubMed  CAS  Google Scholar 

  • Scadden AD, Smith CW (1997) A ribonuclease specific for inosine-containing RNA: a potential role in antiviral defence? EMBO J 16:2140–2149.

    PubMed  CAS  Google Scholar 

  • Scadden AD, Smith CW (2001a) RNAi is antagonized by A–>I hyper-editing. EMBO Rep 2:1107–1111.

    PubMed  CAS  Google Scholar 

  • Scadden AD, Smith CW (2001b) Specific cleavage of hyper-edited dsRNAs. EMBO J 20:4243–4252.

    PubMed  CAS  Google Scholar 

  • Schoft VK, Schopoff S, Jantsch MF (2007) Regulation of glutamate receptor B pre-mRNA splicing by RNA editing. Nucleic Acids Res 35:3723–3732.

    PubMed  CAS  Google Scholar 

  • Seeburg PH, Hartner J (2003) Regulation of ion channel/neurotransmitter receptor function by RNA editing. Curr Opin Neurobiol 13:279–283.

    PubMed  CAS  Google Scholar 

  • Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res Brain Res Rev 26:217–229.

    PubMed  CAS  Google Scholar 

  • Sommer B, Kohler M, Sprengel R, Seeburg PH (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67:11–19.

    PubMed  CAS  Google Scholar 

  • Stefl R, Allain FH (2005) A novel RNA pentaloop fold involved in targeting ADAR2. RNA 11:592–597.

    PubMed  CAS  Google Scholar 

  • Stefl R, Xu M, Skrisovska L, Emeson RB, Allain FH (2006) Structure and specific RNA binding of ADAR2 double-stranded RNA binding motifs. Structure 14:345–355.

    PubMed  CAS  Google Scholar 

  • Stephens OM, Yi-Brunozzi HY, Beal PA (2000) Analysis of the RNA-editing reaction of ADAR2 with structural and fluorescent analogues of the GluR-B R/G editing site. Biochemistry 39:12243–12251.

    PubMed  CAS  Google Scholar 

  • Stephens OM, Haudenschild BL, Beal PA (2004) The binding selectivity of ADAR2’s dsRBMs contributes to RNA-editing selectivity. Chem Biol 11:1239–1250.

    PubMed  CAS  Google Scholar 

  • Strehblow A, Hallegger M, Jantsch MF (2002) Nucleocytoplasmic distribution of human RNA-editing enzyme ADAR1 is modulated by double-stranded RNA-binding domains, a leucine-rich export signal, and a putative dimerization domain. Mol Biol Cell 13:3822–3835.

    PubMed  CAS  Google Scholar 

  • Tanoue A, Koshimizu TA, Tsuchiya M, Ishii K, Osawa M, Saeki M, Tsujimoto G (2002) Two novel transcripts for human endothelin B receptor produced by RNA editing/alternative splicing from a single gene. J Biol Chem 277:33205–33212.

    PubMed  CAS  Google Scholar 

  • Tonkin LA, Bass BL (2003) Mutations in RNAi rescue aberrant chemotaxis of ADAR mutants. Science 302:1725.

    PubMed  CAS  Google Scholar 

  • Tonkin LA, Saccomanno L, Morse DP, Brodigan T, Krause M, Bass BL (2002) RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans. EMBO J 21:6025–6035.

    PubMed  CAS  Google Scholar 

  • Vitali P, Basyuk E, Le Meur E, Bertrand E, Muscatelli F, Cavaille J, Huttenhofer A (2005) ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs. J Cell Biol 169:745–753.

    PubMed  CAS  Google Scholar 

  • Wagner RW, Yoo C, Wrabetz L, Kamholz J, Buchhalter J, Hassan NF, Khalili K, Kim SU, Perussia B, McMorris FA et al. (1990) Double-stranded RNA unwinding and modifying activity is detected ubiquitously in primary tissues and cell lines. Mol Cell Biol 10:5586–5590.

    PubMed  CAS  Google Scholar 

  • Wang Q, O’Brien PJ, Chen CX, Cho DS, Murray JM, Nishikura K (2000) Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors. J Neurochem 74:1290–1300.

    Article  PubMed  CAS  Google Scholar 

  • Wang Q, Miyakoda M, Yang W, Khillan J, Stachura DL, Weiss MJ, Nishikura K (2004) Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem 279:4952–4961.

    PubMed  CAS  Google Scholar 

  • Wang Q, Zhang Z, Blackwell K, Carmichael GG (2005) Vigilins bind to promiscuously A-to-I-edited RNAs and are involved in the formation of heterochromatin. Curr Biol 15:384–391.

    PubMed  CAS  Google Scholar 

  • Wong SK, Sato S, Lazinski DW (2001) Substrate recognition by ADAR1 and ADAR2. RNA 7:846–858.

    PubMed  CAS  Google Scholar 

  • Wu H, Henras A, Chanfreau G, Feigon J (2004) Structural basis for recognition of the AGNN tetraloop RNA fold by the double-stranded RNA-binding domain of Rnt1p RNase III. Proc Natl Acad Sci USA 101:8307–8312.

    PubMed  CAS  Google Scholar 

  • Xia S, Yang J, Su Y, Qian J, Ma E, Haddad GG (2005) Identification of new targets of Drosophila pre-mRNA adenosine deaminase. Physiol Genomics 20:195–202.

    PubMed  CAS  Google Scholar 

  • Yang JH, Nie Y, Zhao Q, Su Y, Pypaert M, Su H, Rabinovici R (2003) Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation. J Biol Chem 278:45833–45842.

    PubMed  CAS  Google Scholar 

  • Yang W, Wang Q, Kanes SJ, Murray JM, Nishikura K (2004) Altered RNA editing of serotonin 5-HT2C receptor induced by interferon: implications for depression associated with cytokine therapy. Brain Res Mol Brain Res 124:70–78.

    PubMed  CAS  Google Scholar 

  • Yang W, Wang Q, Howell KL, Lee JT, Cho DS, Murray JM, Nishikura K (2005) ADAR1 RNA deaminase limits short interfering RNA efficacy in mammalian cells. J Biol Chem 280:3946–3953.

    PubMed  CAS  Google Scholar 

  • Yang W, Chendrimada TP, Wang Q, Higuchi M, Seeburg PH, Shiekhattar R, Nishikura K (2006) Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol 13:13–21.

    PubMed  CAS  Google Scholar 

  • Yi-Brunozzi HY, Stephens OM, Beal PA (2001) Conformational changes that occur during an RNA-editing adenosine deamination reaction. J Biol Chem 276:37827–37833.

    PubMed  CAS  Google Scholar 

  • Zhang Z, Carmichael GG (2001) The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell 106:465–475.

    PubMed  CAS  Google Scholar 

  • Zorio DA, Bentley DL (2004) The link between mRNA processing and transcription: communication works both ways. Exp Cell Res 296:91–97.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 1, 1030, Vienna, Austria

    Michael F. Jantsch

  2. Department of Molecular Biology & Functional Genomics, Stockholm University, S-106 91, Stockholm, Sweden

    Marie Öhman

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  1. Michael F. Jantsch
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  2. Marie Öhman
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Editors and Affiliations

  1. Institute of Microbiology and Genetics, Technical University Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Germany

    H. Ulrich Göringer

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Jantsch, M.F., Öhman, M. (2008). RNA Editing by Adenosine Deaminases that Act on RNA (ADARs). In: Göringer, H.U. (eds) RNA Editing. Nucleic Acids and Molecular Biology, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73787-2_3

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