MicroRNA-directed siRNA biogenesis in Caenorhabditis elegans

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 e...

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Bibliographic Details
Published in:PLoS genetics 2010-04, Vol.6 (4), p.e1000903-e1000903
Main Authors: Corrêa, Régis L, Steiner, Florian A, Berezikov, Eugene, Ketting, René F
Format: Article
Language:English
Subjects:
Animals
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Genetic aspects
Genetics
Genetics and Genomics/Animal Genetics
MicroRNA
MicroRNAs - metabolism
Molecular Biology/mRNA Stability
Molecular Biology/RNA-Protein Interactions
Nematodes
Physiological aspects
Proteins
Ribonuclease III - genetics
Ribonuclease III - metabolism
Ribonucleic acid
RNA
RNA Interference
RNA, Messenger - metabolism
RNA, Small Interfering - metabolism
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1000903