• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of rnaThe RNA SocietyeTOC AlertsSubscriptionsJournal HomeCSHL PressRNA
RNA. Jun 2001; 7(6): 846–858.
PMCID: PMC1370134

Substrate recognition by ADAR1 and ADAR2.


RNA editing catalyzed by ADAR1 and ADAR2 involves the site-specific conversion of adenosine to inosine within imperfectly duplexed RNA. ADAR1- and ADAR2-mediated editing occurs within transcripts of glutamate receptors (GluR) in the brain and in hepatitis delta virus (HDV) RNA in the liver. Although the Q/R site within the GluR-B premessage is edited more efficiently by ADAR2 than it is by ADAR1, the converse is true for the +60 site within this same transcript. ADAR1 and ADAR2 are homologs having two common functional regions, an N-terminal double-stranded RNA-binding domain and a C-terminal deaminase domain. It is neither understood why only certain adenosines within a substrate molecule serve as targets for ADARs, nor is it known which domain of an ADAR confers its specificity for particular editing sites. To assess the importance of several aspects of RNA sequence and structure on editing, we evaluated 20 different mutated substrates, derived from four editing sites, for their ability to be edited by either ADAR1 or ADAR2. We found that when these derivatives contained an A:C mismatch at the editing site, editing by both ADARs was enhanced compared to when A:A or A:G mismatches or A:U base pairs occurred at the same site. Hence substrate recognition and/or catalysis by ADARs could involve the base that opposes the edited adenosine. In addition, by using protein chimeras in which the deaminase domains were exchanged between ADAR1 and ADAR2, we found that this domain played a dominant role in defining the substrate specificity of the resulting enzyme.

Full Text

The Full Text of this article is available as a PDF (1.1M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bass BL, Weintraub H. A developmentally regulated activity that unwinds RNA duplexes. Cell. 1987 Feb 27;48(4):607–613. [PubMed]
  • Bass BL, Weintraub H. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell. 1988 Dec 23;55(6):1089–1098. [PubMed]
  • Berger J, Hauber J, Hauber R, Geiger R, Cullen BR. Secreted placental alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells. Gene. 1988 Jun 15;66(1):1–10. [PubMed]
  • Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature. 1997 May 15;387(6630):303–308. [PubMed]
  • Casey JL, Bergmann KF, Brown TL, Gerin JL. Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7149–7153. [PMC free article] [PubMed]
  • Casey JL, Gerin JL. Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA. J Virol. 1995 Dec;69(12):7593–7600. [PMC free article] [PubMed]
  • Chang FL, Chen PJ, Tu SJ, Wang CJ, Chen DS. The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8490–8494. [PMC free article] [PubMed]
  • Chen CX, Cho DS, Wang Q, Lai F, Carter KC, Nishikura K. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA. 2000 May;6(5):755–767. [PMC free article] [PubMed]
  • Dabiri GA, Lai F, Drakas RA, Nishikura K. Editing of the GLuR-B ion channel RNA in vitro by recombinant double-stranded RNA adenosine deaminase. EMBO J. 1996 Jan 2;15(1):34–45. [PMC free article] [PubMed]
  • Gerber A, Grosjean H, Melcher T, Keller W. Tad1p, a yeast tRNA-specific adenosine deaminase, is related to the mammalian pre-mRNA editing enzymes ADAR1 and ADAR2. EMBO J. 1998 Aug 17;17(16):4780–4789. [PMC free article] [PubMed]
  • Gerber AP, Keller W. An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science. 1999 Nov 5;286(5442):1146–1149. [PubMed]
  • Higuchi M, Maas S, Single FN, Hartner J, Rozov A, Burnashev N, Feldmeyer D, Sprengel R, Seeburg PH. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature. 2000 Jul 6;406(6791):78–81. [PubMed]
  • Higuchi M, Single FN, Köhler M, Sommer B, Sprengel R, Seeburg PH. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell. 1993 Dec 31;75(7):1361–1370. [PubMed]
  • Kim U, Wang Y, Sanford T, Zeng Y, Nishikura K. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11457–11461. [PMC free article] [PubMed]
  • Kuo MY, Chao M, Taylor J. Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol. 1989 May;63(5):1945–1950. [PMC free article] [PubMed]
  • Lai F, Drakas R, Nishikura K. Mutagenic analysis of double-stranded RNA adenosine deaminase, a candidate enzyme for RNA editing of glutamate-gated ion channel transcripts. J Biol Chem. 1995 Jul 21;270(29):17098–17105. [PubMed]
  • Lazinski DW, Taylor JM. Expression of hepatitis delta virus RNA deletions: cis and trans requirements for self-cleavage, ligation, and RNA packaging. J Virol. 1994 May;68(5):2879–2888. [PMC free article] [PubMed]
  • Le SY, Zuker M. Predicting common foldings of homologous RNAs. J Biomol Struct Dyn. 1991 Apr;8(5):1027–1044. [PubMed]
  • Lehmann KA, Bass BL. The importance of internal loops within RNA substrates of ADAR1. J Mol Biol. 1999 Aug 6;291(1):1–13. [PubMed]
  • Liu Y, George CX, Patterson JB, Samuel CE. 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. 1997 Feb 14;272(7):4419–4428. [PubMed]
  • Liu Y, Samuel CE. Mechanism of interferon action: functionally distinct RNA-binding and catalytic domains in the interferon-inducible, double-stranded RNA-specific adenosine deaminase. J Virol. 1996 Mar;70(3):1961–1968. [PMC free article] [PubMed]
  • Lomeli H, Mosbacher J, Melcher T, Höger T, Geiger JR, Kuner T, Monyer H, Higuchi M, Bach A, Seeburg PH. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science. 1994 Dec 9;266(5191):1709–1713. [PubMed]
  • Maas S, Gerber AP, Rich A. Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8895–8900. [PMC free article] [PubMed]
  • Maas S, Melcher T, Herb A, Seeburg PH, Keller W, Krause S, Higuchi M, O'Connell MA. Structural requirements for RNA editing in glutamate receptor pre-mRNAs by recombinant double-stranded RNA adenosine deaminase. J Biol Chem. 1996 May 24;271(21):12221–12226. [PubMed]
  • Martin FH, Castro MM, Aboul-ela F, Tinoco I., Jr Base pairing involving deoxyinosine: implications for probe design. Nucleic Acids Res. 1985 Dec 20;13(24):8927–8938. [PMC free article] [PubMed]
  • Melcher T, Maas S, Herb A, Sprengel R, Higuchi M, Seeburg PH. RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J Biol Chem. 1996 Dec 13;271(50):31795–31798. [PubMed]
  • Melcher T, Maas S, Herb A, Sprengel R, Seeburg PH, Higuchi M. A mammalian RNA editing enzyme. Nature. 1996 Feb 1;379(6564):460–464. [PubMed]
  • O'Connell MA, Krause S, Higuchi M, Hsuan JJ, Totty NF, Jenny A, Keller W. Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol Cell Biol. 1995 Mar;15(3):1389–1397. [PMC free article] [PubMed]
  • Patterson JB, Samuel CE. 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. 1995 Oct;15(10):5376–5388. [PMC free article] [PubMed]
  • Polson AG, Bass BL, Casey JL. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature. 1996 Apr 4;380(6573):454–456. [PubMed]
  • Sommer B, Köhler M, Sprengel R, Seeburg PH. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991 Oct 4;67(1):11–19. [PubMed]
  • Stephens OM, Yi-Brunozzi HY, Beal PA. Analysis of the RNA-editing reaction of ADAR2 with structural and fluorescent analogues of the GluR-B R/G editing site. Biochemistry. 2000 Oct 10;39(40):12243–12251. [PubMed]
  • Wang Q, Khillan J, Gadue P, Nishikura K. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science. 2000 Dec 1;290(5497):1765–1768. [PubMed]
  • Yang JH, Sklar P, Axel R, Maniatis T. Editing of glutamate receptor subunit B pre-mRNA in vitro by site-specific deamination of adenosine. Nature. 1995 Mar 2;374(6517):77–81. [PubMed]

Articles from RNA are provided here courtesy of The RNA Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...