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PMID: 15337849 Published · ppublish English Journal Article

Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis.

RNA (New York, N.Y.) ·Vol. 10 ·No. 10 ·2004-10-00 ·Pages 1518-25

Pillai RS, Artus CG, Filipowicz W

Abstract

MicroRNAs (miRNAs) are approximately 21-nt-long RNAs involved in regulating development, differentiation, and other processes in eukaryotes. In metazoa, nearly all miRNAs control gene expression by imperfectly base-pairing with the 3'-untranslated region (3'-UTR) of target mRNAs and repressing protein synthesis by an unknown mechanism. It is also unknown whether miRNA-mRNA duplexes containing mismatches and bulges provide specific features that are recognized by factors mediating the repression. miRNAs form part of ribonucleoprotein complexes, miRNPs, that contain Argonaute (Ago) and other proteins. Here we demonstrate that effects of miRNAs on translation can be mimicked in human HeLa cells by the miRNA-independent tethering of Ago proteins to the 3'-UTR of a reporter mRNA. Inhibition of protein synthesis occurred without a change in the reporter mRNA level and was dependent on the number, but not the position, of the hairpins tethering hAgo2 to the 3'-UTR. These findings indicate that a primary function of miRNAs is to guide their associated proteins to the mRNA.

MeSH Terms
3' Untranslated Regions Argonaute Proteins Eukaryotic Initiation Factor-2 Genes, Reporter HeLa Cells Humans In Vitro Techniques MicroRNAs/genetics,metabolism Mutation Peptide Initiation Factors/genetics,metabolism Protein Biosynthesis Proteins/genetics,metabolism RNA Interference RNA, Messenger/genetics,metabolism
Chemicals
3' Untranslated Regions AGO2 protein, human Argonaute Proteins Eukaryotic Initiation Factor-2 MicroRNAs PIWIL1 protein, human Peptide Initiation Factors Proteins RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pillai Ramesh S
Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, 4002 Basel, Switzerland.
Artus Caroline G
Filipowicz Witold
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Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1355-8382
DOI
10.1261/rna.7131604
Published
2004-10-00
Epub
2004-00-30
Pages
1518-25
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC1370638
Subset
IM
External Links
PubMed source DOI: 10.1261/rna.7131604 PMC Full Text View journal details
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