Work

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

Year: 2004

Type: article

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.

Source: RNA

DOI: 10.1261/rna.7131604

Authors: RAMESH S. PILLAI, CAROLINE G. ARTUS, WITOLD FILIPOWICZ

Institution: Friedrich Miescher Institute

Language: English

Topic: MicroRNA in disease regulation

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: bronze

Funder: Friedrich Miescher Institute for Biomedical Research

OpenAlex ID: W2163298186