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Translation Block

MicroRNAs (miRNAs) are small, noncoding RNA genes that are found in the genomes of most eukaryotes, where they play an important role in the regulation of gene expression. Although whether gene activity is repressed by blocking translation of messenger RNA (mRNA) targets, or by promoting their deadenylation and then degradation, has been open to debate. Bazzini et al. (p. 233, published online 15 March) and Djuranovic et al. (p. 237) looked at early points in the repression reaction in the zebrafish embryo or in Drosophila tissue culture cells, respectively, and found that translation was blocked before target mRNAs were significantly deadenylated and degraded. Thus, miRNAs appear to interfere with the initiation step of translation.

Abstract

microRNAs (miRNAs) regulate gene expression through translational repression and/or messenger RNA (mRNA) deadenylation and decay. Because translation, deadenylation, and decay are closely linked processes, it is important to establish their ordering and thus to define the molecular mechanism of silencing. We have investigated the kinetics of these events in miRNA-mediated gene silencing by using a Drosophila S2 cell-based controllable expression system and show that mRNAs with both natural and engineered 3′ untranslated regions with miRNA target sites are first subject to translational inhibition, followed by effects on deadenylation and decay. We next used a natural translational elongation stall to show that miRNA-mediated silencing inhibits translation at an early step, potentially translation initiation.
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Supplementary Material

Summary

Materials and Methods
Figs. S1 to S11
Tables S1 to S4
References

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File (djuranovic.sm.pdf)

References and Notes

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Information & Authors

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Published In

Science
Volume 336Issue 607813 April 2012
Pages: 237 - 240
PubMed: 22499947

History

Received: 24 October 2011
Accepted: 13 March 2012

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Acknowledgments

We thank K. Wehner, J. Doudna, M. Jinek, N. Guydosh, and J. Coller for helpful comments. Funding is from HHMI.

Authors

Affiliations

Sergej Djuranovic
Howard Hughes Medical Institute (HHMI) and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ali Nahvi
Howard Hughes Medical Institute (HHMI) and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rachel Green* [email protected]
Howard Hughes Medical Institute (HHMI) and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Notes

*To whom correspondence should be addressed. E-mail: [email protected]

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Science
Volume 336|Issue 6078
13 April 2012
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Received:24 October 2011
Accepted:13 March 2012
Published in print:13 April 2012
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