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Genetics. Jul 2000; 155(3): 1149–1160.
PMCID: PMC1461140

RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary conservation and developmental regulation.

Abstract

Post-transcriptional editing of pre-mRNAs through the action of dsRNA adenosine deaminases results in the modification of particular adenosine (A) residues to inosine (I), which can alter the coding potential of the modified transcripts. We describe here three sites in the para transcript, which encodes the major voltage-activated Na(+) channel polypeptide in Drosophila, where RNA editing occurs. The occurrence of RNA editing at the three sites was found to be developmentally regulated. Editing at two of these sites was also conserved across species between the D. melanogaster and D. virilis. In each case, a highly conserved region was found in the intron downstream of the editing site and this region was shown to be complementary to the region of the exonic editing site. Thus, editing at these sites would appear to involve a mechanism whereby the edited exon forms a base-paired secondary structure with the distant conserved noncoding sequences located in adjacent downstream introns, similar to the mechanism shown for A-to-I RNA editing of mammalian glutamate receptor subunits (GluRs). For the third site, neither RNA editing nor the predicted RNA secondary structures were evolutionarily conserved. Transcripts from transgenic Drosophila expressing a minimal editing site construct for this site were shown to faithfully undergo RNA editing. These results demonstrate that Na(+) channel diversity in Drosophila is increased by RNA editing via a mechanism analogous to that described for transcripts encoding mammalian GluRs.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bass BL. RNA editing and hypermutation by adenosine deamination. Trends Biochem Sci. 1997 May;22(5):157–162. [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]
  • Bass BL, Nishikura K, Keller W, Seeburg PH, Emeson RB, O'Connell MA, Samuel CE, Herbert A. A standardized nomenclature for adenosine deaminases that act on RNA. RNA. 1997 Sep;3(9):947–949. [PMC free article] [PubMed]
  • Benne R. RNA editing. The long and the short of it. Nature. 1996 Apr 4;380(6573):391–392. [PubMed]
  • Beverley SM, Wilson AC. Molecular evolution in Drosophila and the higher Diptera II. A time scale for fly evolution. J Mol Evol. 1984;21(1):1–13. [PubMed]
  • Brusa R, Zimmermann F, Koh DS, Feldmeyer D, Gass P, Seeburg PH, Sprengel R. Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Science. 1995 Dec 8;270(5242):1677–1680. [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, 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]
  • Egebjerg J, Kukekov V, Heinemann SF. Intron sequence directs RNA editing of the glutamate receptor subunit GluR2 coding sequence. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10270–10274. [PMC free article] [PubMed]
  • Haerry TE, Gehring WJ. Intron of the mouse Hoxa-7 gene contains conserved homeodomain binding sites that can function as an enhancer element in Drosophila. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13884–13889. [PMC free article] [PubMed]
  • Haerry TE, Gehring WJ. A conserved cluster of homeodomain binding sites in the mouse Hoxa-4 intron functions in Drosophila embryos as an enhancer that is directly regulated by Ultrabithorax. Dev Biol. 1997 Jun 1;186(1):1–15. [PubMed]
  • Hauck B, Gehring WJ, Walldorf U. Functional analysis of an eye specific enhancer of the eyeless gene in Drosophila. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):564–569. [PMC free article] [PubMed]
  • Herb A, Higuchi M, Sprengel R, Seeburg PH. Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1875–1880. [PMC free article] [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]
  • Hurst SR, Hough RF, Aruscavage PJ, Bass BL. Deamination of mammalian glutamate receptor RNA by Xenopus dsRNA adenosine deaminase: similarities to in vivo RNA editing. RNA. 1995 Dec;1(10):1051–1060. [PMC free article] [PubMed]
  • Keegan LP, Haerry TE, Crotty DA, Packer AI, Wolgemuth DJ, Gehring WJ. A sequence conserved in vertebrate Hox gene introns functions as an enhancer regulated by posterior homeotic genes in Drosophila imaginal discs. Mech Dev. 1997 May;63(2):145–157. [PubMed]
  • Kemp BE, Pearson RB. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342–346. [PubMed]
  • Kennelly PJ, Krebs EG. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991 Aug 25;266(24):15555–15558. [PubMed]
  • Köhler M, Burnashev N, Sakmann B, Seeburg PH. Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing. Neuron. 1993 Mar;10(3):491–500. [PubMed]
  • Kumar M, Carmichael GG. Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3542–3547. [PMC free article] [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]
  • Li M, West JW, Numann R, Murphy BJ, Scheuer T, Catterall WA. Convergent regulation of sodium channels by protein kinase C and cAMP-dependent protein kinase. Science. 1993 Sep 10;261(5127):1439–1442. [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]
  • Polson AG, Bass BL. Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase. EMBO J. 1994 Dec 1;13(23):5701–5711. [PMC free article] [PubMed]
  • Lou L, Bergson C, McGinnis W. Deformed expression in the Drosophila central nervous system is controlled by an autoactivated intronic enhancer. Nucleic Acids Res. 1995 Sep 11;23(17):3481–3487. [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]
  • Saccomanno L, Bass BL. A minor fraction of basic fibroblast growth factor mRNA is deaminated in Xenopus stage VI and matured oocytes. RNA. 1999 Jan;5(1):39–48. [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]
  • Semenov EP, Pak WL. Diversification of Drosophila chloride channel gene by multiple posttranscriptional mRNA modifications. J Neurochem. 1999 Jan;72(1):66–72. [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]
  • Simpson L, Emeson RB. RNA editing. Annu Rev Neurosci. 1996;19:27–52. [PubMed]
  • Morse DP, Bass BL. Detection of inosine in messenger RNA by inosine-specific cleavage. Biochemistry. 1997 Jul 15;36(28):8429–8434. [PubMed]
  • Smith RD, Goldin AL. Phosphorylation of brain sodium channels in the I--II linker modulates channel function in Xenopus oocytes. J Neurosci. 1996 Mar 15;16(6):1965–1974. [PubMed]
  • Morse DP, Bass BL. Long RNA hairpins that contain inosine are present in Caenorhabditis elegans poly(A)+ RNA. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6048–6053. [PMC free article] [PubMed]
  • Smith RD, Goldin AL. Phosphorylation at a single site in the rat brain sodium channel is necessary and sufficient for current reduction by protein kinase A. J Neurosci. 1997 Aug 15;17(16):6086–6093. [PubMed]
  • Murphy BJ, Rogers J, Perdichizzi AP, Colvin AA, Catterall WA. cAMP-dependent phosphorylation of two sites in the alpha subunit of the cardiac sodium channel. J Biol Chem. 1996 Nov 15;271(46):28837–28843. [PubMed]
  • Smith LA, Wang X, Peixoto AA, Neumann EK, Hall LM, Hall JC. A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects. J Neurosci. 1996 Dec 15;16(24):7868–7879. [PubMed]
  • Nishikura K, Yoo C, Kim U, Murray JM, Estes PA, Cash FE, Liebhaber SA. Substrate specificity of the dsRNA unwinding/modifying activity. EMBO J. 1991 Nov;10(11):3523–3532. [PMC free article] [PubMed]
  • Thackeray JR, Ganetzky B. Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para. Genetics. 1995 Sep;141(1):203–214. [PMC free article] [PubMed]
  • O'Dowd DK, Gee JR, Smith MA. Sodium current density correlates with expression of specific alternatively spliced sodium channel mRNAs in single neurons. J Neurosci. 1995 May;15(5 Pt 2):4005–4012. [PubMed]
  • Wagner RW, Smith JE, Cooperman BS, Nishikura K. A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2647–2651. [PMC free article] [PubMed]
  • Patton DE, Silva T, Bezanilla F. RNA editing generates a diverse array of transcripts encoding squid Kv2 K+ channels with altered functional properties. Neuron. 1997 Sep;19(3):711–722. [PubMed]
  • Petschek JP, Scheckelhoff MR, Mermer MJ, Vaughn JC. RNA editing and alternative splicing generate mRNA transcript diversity from the Drosophila 4f-rnp locus. Gene. 1997 Dec 19;204(1-2):267–276. [PubMed]

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