Drosophila miR2 primarily targets the m7GpppN cap structure for translational repression.

Full Abstract

Understanding the molecular mechanism(s) of how miRNAs repress mRNA translation is a fundamental challenge in RNA biology. Here we use a validated cell-free system from Drosophila embryos to investigate how miR2 inhibits translation initiation. By screening a library of chemical m7GpppN cap structure analogs, we identified defined modifications of the triphosphate backbone that augment miRNA-mediated inhibition of translation initiation but are "neutral" toward general cap-dependent translation. Interestingly, these caps also augment inhibition by 4E-BP. Kinetic dissection of translational repression and miR2-induced deadenylation shows that both processes proceed largely independently, with establishment of the repressed state involving a slow step. Our data demonstrate a primary role for the m7GpppN cap structure in miRNA-mediated translational inhibition, implicate structural determinants outside the core eIF4E-binding region in this process, and suggest that miRNAs may target cap-dependent translation through a mechanism related to the 4E-BP class of translational regulators.

Author information

Author/s: Zdanowicz, Agnieszka (A); Thermann, Rolf (R); Kowalska, Joanna (J); Jemielity, Jacek (J); Duncan, Kent (K); Preiss, Thomas (T); Darzynkiewicz, Edward (E); Hentze, Matthias W (MW);

Affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany.

Grants: 55005604 (Agency:Howard Hughes Medical Institute)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Molecular cell (Mol Cell), published in United States. (Language: eng)

Reference: 2009-Sep; vol 35 (issue 6) : pp 881-8

Dates: Created 2009/09/28; Completed 2009/10/08;

PMID: 19782035, status: MEDLINE (last retrieval date: 10/8/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Binding Sites
Cell-Free System
Cells, Cultured
Drosophila Proteins - genetics; metabolism
Drosophila melanogaster - embryology; genetics; metabolism
Gene Expression Regulation, Developmental
Gene Silencing

Kinetics
MicroRNAs - metabolism
Protein Biosynthesis
Pyrophosphatases - metabolism
RNA Caps - metabolism
RNA Stability
RNA-Induced Silencing Complex - genetics; metabolism
Transfection

Associated Chemicals: Drosophila Proteins (0) ; MicroRNAs (0) ; RNA Caps (0) ; RNA-Induced Silencing Complex (0) ; cup protein, Drosophila (0) ; Pyrophosphatases (EC 3.6.1.-) ; m(7)G(5')pppN pyrophosphatase (EC 3.6.1.30)

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