Drosophila Micrornas Are Sorted into Functionally Distinct Argonaute Complexes After Production by Dicer-1.
From: Gene Center and Munich Center for Integrated Protein Science (CiPS(M)), Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
Cell
- Publish Date: Jul 2007
- ISSN: 0092-8674
- Volume: 130
- Issue: 2
- Pages: 287-97
- Medium: Print
- Language: English
- Citation (JAMA): Förstemann Klaus, Horwich Michael D, Wee Liangmeng, et al. Drosophila Micrornas Are Sorted into Functionally Distinct Argonaute Complexes After Production by Dicer-1.. Cell Jul 2007;130:287-97
Abstract
Small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide distinct classes of RNA-induced silencing complexes (RISCs) to repress mRNA expression in biological processes ranging from development to antiviral defense. In Drosophila, separate but conceptually similar endonucleolytic pathways produce siRNAs and miRNAs. Here, we show that despite their distinct biogenesis, double-stranded miRNAs and siRNAs participate in a common sorting step that partitions them into Ago1- or Ago2-containing effector complexes. These distinct complexes silence their target RNAs by different mechanisms. miRNA-loaded Ago2-RISC mediates RNAi, but only Ago1 is able to repress an mRNA with central mismatches in its miRNA-binding sites. Conversely, Ago1 cannot mediate RNAi, because it is an inefficient nuclease whose catalytic rate is limited by the dissociation of its reaction products. Thus, the two members of the Drosophila Ago subclade of Argonaute proteins are functionally specialized, but specific small RNA classes are not restricted to associate with Ago1 or Ago2.
Mesh Headings (Keywords): Animals, Binding Sites, Drosophila Proteins, Drosophila melanogaster, Gene Silencing, Genes, Reporter, Kinetics, MicroRNAs, Models, Biological, RNA Helicases, RNA Transport, RNA, Messenger, RNA-Induced Silencing Complex
Check for Full Text / PubMed Unique Identifier (PMID): 17662943
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