Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7.
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.
Fischer
Sylvia E J
SE
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Butler
Maurice D
MD
Pan
Qi
Q
Ruvkun
Gary
G
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
D029742:Caenorhabditis elegans Proteins; C532532:ERI-6 protein, C elegans; C532531:ERI-7 protein, C elegans; D004265:DNA Helicases
Nature. 2001 Jan 18;409(6818):363-6
11201747
Trends Biochem Sci. 2006 Nov;31(11):622-30
17029813
Chromosome Res. 2007;15(5):607-21
17674149
Nature. 2004 Feb 12;427(6975):645-9
14961122
Cell. 1988 Nov 18;55(4):567-76
2846184
Nature. 2005 Jul 28;436(7050):593-7
16049496
Nature. 2003 Jan 16;421(6920):231-7
12529635
Science. 2005 Sep 2;309(5740):1519-24
16141061
Nat Genet. 2000 Feb;24(2):180-3
10655066
RNA. 2006 Apr;12(4):589-97
16489184
Curr Biol. 2006 Mar 21;16(6):580-5
16546082
Science. 2007 Jan 12;315(5809):241-4
17124291
Cell. 2006 Jan 27;124(2):343-54
16439208
Curr Biol. 2002 Aug 6;12(15):1317-9
12176360
Curr Biol. 2004 Jan 20;14(2):R75-7
14738755
Dev Biol. 2002 Apr 1;244(1):170-9
11900466
Nature. 2004 Sep 16;431(7006):338-42
15372040
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9724-9
11493677
Nature. 2001 Feb 22;409(6823):1000
11234000
Nature. 2000 Nov 16;408(6810):325-30
11099033
Annu Rev Biochem. 2002;71:817-46
12045112
Mol Cell. 2002 Oct;10(4):809-17
12419225
Curr Biol. 2005 Dec 6;15(23):2149-55
16289642
Nature. 2005 Aug 18;436(7053):1044-7
16107852
Cell. 1999 Oct 15;99(2):133-41
10535732
Cell. 1999 Oct 15;99(2):123-32
10535731
Genes Dev. 2003 Oct 15;17(20):2496-501
14522953
Cell. 2002 Jun 28;109(7):861-71
12110183
Cell. 2004 Mar 19;116(6):831-41
15035985
WormBook. 2006 Feb 11;:1-11
18050451
Cell. 2001 Nov 16;107(4):465-76
11719187
J Cell Biol. 1998 Apr 6;141(1):297-308
9531567
Nat Biotechnol. 2004 Dec;22(12):1567-72
15558047
Gene. 2001 Jan 24;263(1-2):103-12
11223248
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18420-4
16339901
Cell. 2006 Nov 17;127(4):747-57
17110334
RNA. 2003 Jan;9(1):25-32
12554873
EMBO J. 2001 Apr 17;20(8):2069-78
11296239
Nat Genet. 2001 Jun;28(2):160-4
11381264
Nature. 1997 Oct 23;389(6653):870-6
9349821
Hum Mol Genet. 2002 Jan 15;11(2):175-84
11809726
Genes Dev. 1995 Dec 15;9(24):3149-62
8543158