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.


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


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


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References and Notes

Bartel D. P., MicroRNAs: Target recognition and regulatory functions. Cell 136, 215 (2009).
Bagga S., et al., Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122, 553 (2005).
Lim L. P., et al., Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769 (2005).
Giraldez A. J., et al., Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75 (2006); 10.1126/science.1122689.
Eulalio A., et al., Deadenylation is a widespread effect of miRNA regulation. RNA 15, 21 (2009).
Beilharz T. H., et al., microRNA-mediated messenger RNA deadenylation contributes to translational repression in mammalian cells. PLoS ONE 4, e6783 (2009).
Olsen P. H., Ambros V., The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev. Biol. 216, 671 (1999).
Pillai R. S., et al., Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309, 1573 (2005); 10.1126/science.1115079.
Petersen C. P., Bordeleau M. E., Pelletier J., Sharp P. A., Short RNAs repress translation after initiation in mammalian cells. Mol. Cell 21, 533 (2006).
Ding X. C., Grosshans H., Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteins. EMBO J. 28, 213 (2009).
Hendrickson D. G., et al., Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA. PLoS Biol. 7, e1000238 (2009).
Guo H., Ingolia N. T., Weissman J. S., Bartel D. P., Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466, 835 (2010).
Wu L., Fan J., Belasco J. G., MicroRNAs direct rapid deadenylation of mRNA. Proc. Natl. Acad. Sci. U.S.A. 103, 4034 (2006).
Wakiyama M., Takimoto K., Ohara O., Yokoyama S., Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system. Genes Dev. 21, 1857 (2007).
Mathonnet G., et al., MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317, 1764 (2007).
Zdanowicz A., et al., Drosophila miR2 primarily targets the m7GpppN cap structure for translational repression. Mol. Cell 35, 881 (2009).
Fabian M. R., et al., Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Mol. Cell 35, 868 (2009).
Johansen H., et al., Regulated expression at high copy number allows production of a growth-inhibitory oncogene product in Drosophila Schneider cells. Genes Dev. 3, 882 (1989).
Nahvi A., Shoemaker C. J., Green R., An expanded seed sequence definition accounts for full regulation of the hid 3′ UTR by bantam miRNA. RNA 15, 814 (2009).
Behm-Ansmant I., et al., mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev. 20, 1885 (2006).
Selvaraj A., et al., Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes. Genes Dev. 19, 891 (2005).
Gallie D. R., The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency. Genes Dev. 5, 2108 (1991).
Beilharz T. H., Preiss T., Widespread use of poly(A) tail length control to accentuate expression of the yeast transcriptome. RNA 13, 982 (2007).
Muckenthaler M., Gunkel N., Stripecke R., Hentze M. W., Regulated poly(A) tail shortening in somatic cells mediated by cap-proximal translational repressor proteins and ribosome association. RNA 3, 983 (1997).
Iwasaki S., Kawamata T., Tomari Y., Drosophila argonaute1 and argonaute2 employ distinct mechanisms for translational repression. Mol. Cell 34, 58 (2009).
Marzluff W. F., Wagner E. J., Duronio R. J., Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail. Nat. Rev. Genet. 9, 843 (2008).
Braun J. E., Huntzinger E., Fauser M., Izaurralde E., GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. Mol. Cell 44, 120 (2011).
Chekulaeva M., et al., miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs. Nat. Struct. Mol. Biol. 18, 1218 (2011).
Fabian M. R., et al., miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nat. Struct. Mol. Biol. 18, 1211 (2011).
Kuroha K., et al., Receptor for activated C kinase 1 stimulates nascent polypeptide-dependent translation arrest. EMBO Rep. 11, 956 (2010).

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Published In

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


Received: 24 October 2011
Accepted: 13 March 2012


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



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.


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

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