RRC ID 46581
著者 Corrêa RL, Steiner FA, Berezikov E, Ketting RF.
タイトル MicroRNA-directed siRNA biogenesis in Caenorhabditis elegans.
ジャーナル PLoS Genet
Abstract RNA interference (RNAi) is a post-transcriptional silencing process, triggered by double-stranded RNA (dsRNA), leading to the destabilization of homologous mRNAs. A distinction has been made between endogenous RNAi-related pathways and the exogenous RNAi pathway, the latter being essential for the experimental use of RNAi. Previous studies have shown that, in Caenorhabditis elegans, a complex containing the enzymes Dicer and the Argonaute RDE-1 process dsRNA. Dicer is responsible for cleaving dsRNA into short interfering RNAs (siRNAs) while RDE-1 acts as the siRNA acceptor. RDE-1 then guides a multi-protein complex to homologous targets to trigger mRNA destabilization. However, endogenous role(s) for RDE-1, if any, have remained unexplored. We here show that RDE-1 functions as a scavenger protein, taking up small RNA molecules from many different sources, including the microRNA (miRNA) pathway. This is in striking contrast to Argonaute proteins functioning directly in the miRNA pathway, ALG-1 and ALG-2: these proteins exclusively bind miRNAs. While playing no significant role in the biogenesis of the main pool of miRNAs, RDE-1 binds endogenous miRNAs and triggers RdRP activity on at least one perfectly matching, endogenous miRNA target. The resulting secondary siRNAs are taken up by a set of Argonaute proteins known to act as siRNA acceptors in exogenous RNAi, resulting in strong mRNA destabilization. Our results show that RDE-1 in an endogenous setting is actively screening the transcriptome using many different small RNAs, including miRNAs, as a guide, with implications for the evolution of transcripts with a potential to be recognized by Dicer.
巻・号 6(4)
ページ e1000903
公開日 2010-4-8
DOI 10.1371/journal.pgen.1000903
PMID 20386745
PMC PMC2851571
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism MicroRNAs / metabolism* RNA Interference RNA, Messenger / metabolism RNA, Small Interfering / metabolism* Ribonuclease III / genetics Ribonuclease III / metabolism
IF 5.175
引用数 36
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm1195 tm0894 tm1637 tm1019 tm0914