Title

Drosophila microRNAs are sorted into functionally distinct argonaute complexes after production by dicer-1

Student Author(s)

Michael D. Horwich; LiangMeng Wee

GSBS Program

Interdisciplinary Graduate Program

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

7-27-2007

Document Type

Article

Medical Subject Headings

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

Disciplines

Biochemistry | Molecular Biology

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.

Rights and Permissions

Citation: Cell. 2007 Jul 27;130(2):287-97. Link to article on publisher's site

Comments

Co-author Michael Horwich is a student in the MD/PhD program and co-author LiangMeng Wee is a student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

17662943