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PMID: 12154197 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A microRNA in a multiple-turnover RNAi enzyme complex.

Science (New York, N.Y.) ·Vol. 297 ·No. 5589 ·2002-09-20 ·Pages 2056-60

Hutvágner G, Zamore PD

Abstract

In animals, the double-stranded RNA-specific endonuclease Dicer produces two classes of functionally distinct, tiny RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). miRNAs regulate mRNA translation, whereas siRNAs direct RNA destruction via the RNA interference (RNAi) pathway. Here we show that, in human cell extracts, the miRNA let-7 naturally enters the RNAi pathway, which suggests that only the degree of complementarity between a miRNA and its RNA target determines its function. Human let-7 is a component of a previously identified, miRNA-containing ribonucleoprotein particle, which we show is an RNAi enzyme complex. Each let-7-containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Argonaute Proteins Base Pairing Base Sequence Cell Extracts Cytoplasm/metabolism DEAD Box Protein 20 DEAD-box RNA Helicases Drosophila melanogaster/genetics Endoribonucleases/metabolism Eukaryotic Initiation Factor-2 Eukaryotic Initiation Factors Gene Silencing HeLa Cells Humans MicroRNAs Minor Histocompatibility Antigens Models, Genetic Nuclear Proteins/metabolism Peptide Initiation Factors/metabolism Protein Biosynthesis RNA Helicases/metabolism RNA, Antisense/chemistry,metabolism RNA, Double-Stranded/chemistry,metabolism RNA, Messenger/chemistry,metabolism RNA, Small Interfering RNA, Untranslated/chemistry,metabolism RNA-Induced Silencing Complex Ribonuclease III Ribonucleoproteins/metabolism Ribonucleoproteins, Small Nuclear
Chemicals
AGO1 protein, human AGO2 protein, human Argonaute Proteins Cell Extracts Eukaryotic Initiation Factor-2 Eukaryotic Initiation Factors GEMIN4 protein, human MicroRNAs Minor Histocompatibility Antigens Nuclear Proteins Peptide Initiation Factors RNA, Antisense RNA, Double-Stranded RNA, Messenger RNA, Small Interfering RNA, Untranslated RNA-Induced Silencing Complex Ribonucleoproteins Ribonucleoproteins, Small Nuclear Adenosine Triphosphate Endoribonucleases Ribonuclease III DDX20 protein, human DEAD Box Protein 20 DEAD-box RNA Helicases RNA Helicases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hutvágner György
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA.
Zamore Phillip D
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2002-09-20
Epub
2002-00-01
Pages
2056-60
Language
English
Region
United States
NLM ID
0404511
Subset
IM
Grants
NIGMS NIH HHS · GM62862-01 · United States
Corrections
CommentIn
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