RRC ID 46250
Author Zhuang JJ, Banse SA, Hunter CP.
Title The nuclear argonaute NRDE-3 contributes to transitive RNAi in Caenorhabditis elegans.
Journal Genetics
Abstract The Caenorhabditis elegans nuclear RNA interference defective (Nrde) mutants were identified by their inability to silence polycistronic transcripts in enhanced RNAi (Eri) mutant backgrounds. Here, we report additional nrde-3-dependent RNAi phenomena that extend the mechanisms, roles, and functions of nuclear RNAi. We show that nrde-3 mutants are broadly RNAi deficient and that overexpressing NRDE-3 enhances RNAi. Consistent with NRDE-3 being a dose-dependent limiting resource for effective RNAi, we find that NRDE-3 is required for eri-dependent enhanced RNAi phenotypes, although only for a subset of target genes. We then identify pgl-1 as an additional limiting RNAi resource important for eri-dependent silencing of a nonoverlapping subset of target genes, so that an nrde-3; pgl-1; eri-1 triple mutant fails to show enhanced RNAi for any tested gene. These results suggest that nrde-3 and pgl-1 define separate and independent limiting RNAi resource pathways. Limiting RNAi resources are proposed to primarily act via endogenous RNA silencing pathways. Consistent with this, we find that nrde-3 mutants misexpress genes regulated by endogenous siRNAs and incompletely silence repetitive transgene arrays. Finally, we find that nrde-3 contributes to transitive RNAi, whereby amplified silencing triggers act in trans to silence sequence-similar genes. Because nrde-dependent silencing is thought to act in cis to limit the production of primary transcripts, this result reveals an unexpected role for nuclear processes in RNAi silencing.
Volume 194(1)
Pages 117-31
Published 2013-5
DOI 10.1534/genetics.113.149765
PII genetics.113.149765
PMID 23457236
PMC PMC3632460
MeSH Alleles Animals Argonaute Proteins / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism* Exoribonucleases / metabolism Gene Expression Regulation Mutation / genetics Phenotype RNA Interference* RNA, Double-Stranded / metabolism RNA-Binding Proteins / metabolism* Transgenes / genetics
IF 4.075
Times Cited 9
C.elegans tm1860 tm1917 tm1624 tm1276 tm572