Preferences help
enabled [disable] Abstract
Number of results
2004 | 53 | 2 | 147-154
Article title

Funkcjonalne znaczenie redagowania transkryptłw przez deaminazę adenozyny dwuniciowego RNA

Title variants
Functional significance of transcripts editing by double-stranded RNA adenosine deaminases
Languages of publication
Summary Adenosine deaminases that act on RNA (ADARs) convert adenosine to inosine in double-stranded regions of RNA via hydrolytic deamination. As inosines are recognized as guanosines during translation this editing event can lead to a codon exchange in the edited mRNA. The amino acid changes introduced by this A-to-I RNA editing result in significant alterations in the physiological properties of gene products. For instance, editing of the "Q/R" site of AMPA GluR-B subunit dramatically decreases the Ca+2 permeability of the channel. Dramatic changes in the G-protein coupling efficiency of 5-HT2CR as well as in the rates of KV2K1 channel closure have been reported to be consequences of A-to-I RNA editing also. In addition, creation of an alternative splice acceptor site via editing of its own mRNA by ADAR2 has been reported. The A-to-I RNA editing mechanism requires: (1) a doublestranded RNA (dsRNA) structure, usually formed between the exonic editing site and a downstream intron sequence and (2) dsRNA-specific adenosine deaminases. The members of this ADAR gene family appear to share structural similarity, containing two to three repeats of dsRNA-binding domains and a separate deaminase or catalytic domain. Defects in ADAR are a cause of some diseases, for example dyschromatosis symmetrica hereditaria.
Physical description
  • BASS B. L., NISHIKURA K., KELLER W., SEEBURG P. H., EMESON R. B., O'CONNELL M. A., SAMUEL C. E., HERBERT A., 1997. A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3, 947-949.
  • BASS B. L., WEINTRAUB H., 1987. A developmentally regulated activity that unwinds RNA duplexes. Cell 48, 607-613.
  • BURNS C. M., CHU H., RUETER S. M., HUTCHINSON L. K., CANTON H., SANDERS-BUSH E., EMESON R. B., 1997. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387, 303-308.
  • CARMICHAEL G. G., 2003. Antisense starts making more sense. Nat. Biotech. 21, 371-372.
  • CHEN C.-X., CHO D.-S. C., WANG Q., LAI F., CARTER K. C., 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.
  • CHO D.-S., YANG W., LEE J. T., SHIEKHATTAR R., MURRAY J. M., NISHIKURA K., 2003. Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. J. Biol. Chem. 278, 17093-17102.
  • DABIRI G. A., LAI F., DRAKAS R. A., NISHIKURA K., 1996. Editing of the GluR-B ion channel RNA in vitro by recombinant double-stranded RNA adenosine deaminase. EMBO J. 15, 34-45.
  • DINGLEDINE R., BORGES K., BOWIE D., TRAYNELIS S. F. 1999. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7-61.
  • DOYLE M., JANTSCH M. F., 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.
  • ECKMANNC. R., JANTSCH M. F., 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.
  • FELDMEYER D. i współaut. 1999. Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunitGluR-B. Nature Neurosci. 2, 57-64.
  • GALLO A., KEEGAN L. P., RING G. M., O'CONNELL M. A., 2003. An ADAR that edits transcripts encoding ion channel subunits functions as a dimer. EMBO J. 22, 3421-3430.
  • 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.
  • GERBER A., O'CONNELL M. A., KELLER W., 1997. Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette. RNA 3, 453-463.
  • HERBERT A., ALKFEN J., KIM Y. G.,MIAN I. S., 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.
  • HIGUCHI M., MAAS S., SINGLE F.N., HARTNER J., ROZOVS A., BURNASHEVS N., FELDMEYERS D., SPRENGEL R., SEEBURG P.H., 2000. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2.Nature 406, 78-81.
  • HOLLEY R. W., 1965. Structure of an alanine transfer ribonucleic acid. J. Am.Med. Assoc. 194, 868-871.
  • HOUGH R. F., BASS B. L., 1997. Analysis of Xenopus dsRNA adenosine deaminase cDNAs reveals similarities toDNAmethyltransferases. RNA 3, 356-370.
  • HOUGH R. F., LINGMA A. T., BASS B. L., 1999. Caenorhabditis elegans mRNAs that encode a protein similar to ADARs derive from an operon containing six genes. Nucleic Acids Res. 27, 3424-3432
  • HURST S. R., HOUGH R. F., ARUSCAVAGE P. J., BASS B. L. 1995. Deamination of mammalian glutamate receptor RNA by Xenopus dsRNA adenosine deaminase: similarities to in vivo RNA editing. RNA 1, 1051-1060.
  • KIM U.,WANG Y., SANFORD T., 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.
  • KÖHLER M., BURNASHEV N., SAKMANN B., SEEBURG P. H., 1993. Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing. Neuron 10, 491-500.
  • KOHR G., MELCHER T., SEEBURG P. H., 1998. Candidate editases for GluR channels in single neurons of rat. Neuropharmacology 37, 1411-1417.
  • KOMAYA G., 1924. Symmetrische Pigmentanomalie der Extremitaeten. Arch. Derm. Syph. 147, 389-393.
  • LAI F., CHEN C.-X., CARTER K. C., NISHIKURA K., 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.
  • MAAS S. i współaut., 1996. Different structural and enzymatic requirements for RNA editing in glutamate receptor pre-mRNAs. J. Biol. Chem. 271, 12221-12226.
  • MANN M. R., BARTOLOMEI M. S., 1999. Towards a molecular understanding of Prader-Willi and Angelman syndromes. Hum. Mol. Genet. 8, 1867-1873.
  • MELCHER T., MAAS S., HERB A., SPRENGEL R., SEEBURG P. H., HIGUCHI M., 1996. A mammalian RNA editing enzyme. Nature 379, 460-464.
  • MIYAMURA Y., SUZUKI T., KONO M., INAGAKI K., ITO S., SUZUKI N., TOMITA Y., 2003. Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria. Am. J. Hum. Genet. 73, 693-699.
  • MORSE D. P., ARUSCAVAGE J., BASS B. L., 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.
  • NICHOLS R. D., KNEPPER J. L. 2001. Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes. Annu. Rev. Genomics Hum. Genet. 2, 153-175.
  • O'CONNELL M. A., GERBER A., KELLER W. 1997. Purification of human double-stranded RNA-specific editase 1 (hRED1) involved in editing of brain glutamate receptor B pre-mRNA. J. Biol. Chem. 272, 473-478.
  • O'CONNELL M. A., KRAUSE S., HIGUCHI M., HSUAN J. J., TOTTY N., JENNY A., KELLER W., 1995. Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol. Cell. Biol. 15, 1389-1397.
  • PATTON D. E., 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.
  • POLSON A. G., BASS B. L., 1994. Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase. EMBO J. 13, 5701-5711.
  • POLSON A. G., CRAIN P. F., POMERANTZ S. C.,MC CLOSKEY J. A., BASS B. L., 1991. Themechanism of adenosine to inosine conversion by the double-stranded RNA unwinding/modifying activity: a high performance liquid chromatography-mass spectrometry analysis. Biochemistry 30, 11507-11514.
  • REBAGLIATI M. R.,MELTON D. A., 1987. Antisense RNA injections into fertilized frog eggs reveal an RNA duplex unwinding activity. Cell 48, 599-605.
  • RUETER S.M. , DAWSON T. R., EMESON R. B., 1999. Regulation of alternative splicing by RNA editing. Nature 399, 75-80.
  • SACCOMANNO L., BASS B.L., 1999. Aminor fraction of basic fibroblast growth factor mRNA is deaminated in Xenopus stage VI and maturated oocytes. RNA 5, 39-48 SANSAM C. L., WELLS K. S., EMESON R. B., 2003. Modulation of RNA editing by functional nucleolar sequestration of ADAR2. Proc. Natl. Acad. Sci. U S A. 100, 14018-1423.
  • SCHWARTZ T., BEHLKE J., LOWENHAUP K., HEINEMANN U., RICH A., 2001. Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins. Nature 8, 761-765.
  • SEEBURG P. H., HIGUCHI M., SPRENGEL R., 1998. RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res. Rev. 26, 217-229.
  • SLAVOV D., CLARK M., GARDINER K., 2000. Comparative analysis of the RED1 and RED2 A-to-I RNA editing genes from mammals, pufferfish and zebrafish. Gene 250, 41-51.
  • SLAVOV D., GARDINER K., 2002. Phylogenetic comparison of the pre-mRNA adenosine deaminase ADAR2 genes and transcripts: conservation and diversity in editing site sequence and alternative splicing patterns. Gene 299, 83-94.
  • SMITH H. C., GOTT J. M., HANSON M. R., 1997. A guide to RNA editing. RNA 3, 1105-1123.
  • SOMMER B., KÖHLER M., SPRENGEL R., SEEBURG P. H., 1991. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67, 11-19.
  • ST JOHNSTON D., BROWN N. H., GALL J. G., JANTSCH M., 1992. A conserved double-stranded RNA-binding domain. Proc. Natl. Acad. Sci. USA. 89, 10979-10983.
  • TONKIN L., A., SACCOMANNO L.,MORSE D. P., BRODIGAN T., KRAUSE M., BASS B. L., 2002. RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans. EMBO J. 21, 6025-6035.
  • TSVETKOV A., JANTSCH M., WU Z., MURPHY C., GALL J. G., 1992. Transcription on lampbrush chromosome loops in the absence of U2 snRNA. Mol. Biol. Cell 3, 249-261.
  • WANG Q., KHILLAN J., GADUE P., NISHIKURA K., 2000. Requirement of the RNA Editing Deaminase ADAR1 Gene for Embryonic Erythropoiesis. Science 290, 1765-1768.
  • WANG Q., MIYAKODA M., YANG W., KHILLAN J., STACHURA D. L., WEISS M. J., NISHIKURA K., 2004. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J. Biol. Chemist. 279, 4952-4961.
  • YELIN R., DAHARY D., SOREK R., LEVANON E. Y., GOLDSTEIN O., SHOSHAN A., DIBER A., BITON S., TAMIR Y., KHOSRAVI R., NEMZER S., PINNER E., WALACH S., BERNSTEIN J., SAVITSKY K., ROTMAN G., 2003. Widespread occurrence of antisense transcription in the human genome. Nat. Biotechnol. 21, 379-386.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.