title: Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7.
abstract: Mutations that enhance the response to double-stranded RNA (dsRNA) have revealed components of the RNA interference (RNAi) pathway or related small RNA pathways. To explore these small RNA pathways, we screened for Caenorhabditis elegans mutants displaying an enhanced response to exogenous dsRNAs. Here we describe the isolation of mutations in two adjacent, divergently transcribed open reading frames (eri-6 and eri-7) that fail to complement. eri-6 and eri-7 produce separate pre-messenger RNAs (pre-mRNAs) that are trans-spliced to form a functional mRNA, eri-6/7. Trans-splicing of eri-6/7 is mediated by a direct repeat that flanks the eri-6 gene. Adenosine to inosine editing within untranslated regions of eri-6 and eri-7 pre-mRNAs reveals a double-stranded pre-mRNA intermediate, forming in the nucleus before splicing occurs. The ERI-6/7 protein is a superfamily I helicase that both negatively regulates the exogenous RNAi pathway and functions in an endogenous RNAi pathway.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Sylvia E J
authors.initials: SE
authors.lastname: Fischer
authors.forename: Maurice D
authors.initials: MD
authors.lastname: Butler
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D017238:Genes, Helminth / Q000235:genetics*; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D034622:RNA Interference / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D020040:Trans-Splicing
chemical_list: D029742:Caenorhabditis elegans Proteins; C532532:ERI-6 protein, C elegans; C532531:ERI-7 protein, C elegans; D004265:DNA Helicases
references.citation: Nature. 2001 Jan 18;409(6818):363-6
references.pmid: 11201747
references.citation: Trends Biochem Sci. 2006 Nov;31(11):622-30
references.pmid: 17029813
references.citation: Chromosome Res. 2007;15(5):607-21
references.pmid: 17674149
references.citation: Nature. 2004 Feb 12;427(6975):645-9
references.pmid: 14961122
references.citation: Cell. 1988 Nov 18;55(4):567-76
references.pmid: 2846184
references.citation: Nature. 2005 Jul 28;436(7050):593-7
references.pmid: 16049496
references.citation: Nature. 2003 Jan 16;421(6920):231-7
references.pmid: 12529635
references.citation: Science. 2005 Sep 2;309(5740):1519-24
references.pmid: 16141061
references.citation: Nat Genet. 2000 Feb;24(2):180-3
references.pmid: 10655066
references.citation: RNA. 2006 Apr;12(4):589-97
references.pmid: 16489184
references.citation: Curr Biol. 2006 Mar 21;16(6):580-5
references.pmid: 16546082
references.citation: Science. 2007 Jan 12;315(5809):241-4
references.pmid: 17124291
references.citation: Cell. 2006 Jan 27;124(2):343-54
references.pmid: 16439208
references.citation: Curr Biol. 2002 Aug 6;12(15):1317-9
references.pmid: 12176360
references.citation: Curr Biol. 2004 Jan 20;14(2):R75-7
references.pmid: 14738755
references.citation: Dev Biol. 2002 Apr 1;244(1):170-9
references.pmid: 11900466
references.citation: Nature. 2004 Sep 16;431(7006):338-42
references.pmid: 15372040
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9724-9
references.pmid: 11493677
references.citation: Nature. 2001 Feb 22;409(6823):1000
references.pmid: 11234000
references.citation: Nature. 2000 Nov 16;408(6810):325-30
references.pmid: 11099033
references.citation: Annu Rev Biochem. 2002;71:817-46
references.pmid: 12045112
references.citation: Mol Cell. 2002 Oct;10(4):809-17
references.pmid: 12419225
references.citation: Curr Biol. 2005 Dec 6;15(23):2149-55
references.pmid: 16289642
references.citation: Nature. 2005 Aug 18;436(7053):1044-7
references.pmid: 16107852
references.citation: Cell. 1999 Oct 15;99(2):133-41
references.pmid: 10535732
references.citation: Cell. 1999 Oct 15;99(2):123-32
references.pmid: 10535731
references.citation: Genes Dev. 2003 Oct 15;17(20):2496-501
references.pmid: 14522953
references.citation: Cell. 2002 Jun 28;109(7):861-71
references.pmid: 12110183
references.citation: Cell. 2004 Mar 19;116(6):831-41
references.pmid: 15035985
references.citation: WormBook. 2006 Feb 11;:1-11
references.pmid: 18050451
references.citation: Cell. 2001 Nov 16;107(4):465-76
references.pmid: 11719187
references.citation: J Cell Biol. 1998 Apr 6;141(1):297-308
references.pmid: 9531567
references.citation: Nat Biotechnol. 2004 Dec;22(12):1567-72
references.pmid: 15558047
references.citation: Gene. 2001 Jan 24;263(1-2):103-12
references.pmid: 11223248
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18420-4
references.pmid: 16339901
references.citation: Cell. 2006 Nov 17;127(4):747-57
references.pmid: 17110334
references.citation: RNA. 2003 Jan;9(1):25-32
references.pmid: 12554873
references.citation: EMBO J. 2001 Apr 17;20(8):2069-78
references.pmid: 11296239
references.citation: Nat Genet. 2001 Jun;28(2):160-4
references.pmid: 11381264
references.citation: Nature. 1997 Oct 23;389(6653):870-6
references.pmid: 9349821
references.citation: Hum Mol Genet. 2002 Jan 15;11(2):175-84
references.pmid: 11809726
references.citation: Genes Dev. 1995 Dec 15;9(24):3149-62
references.pmid: 8543158