MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F

Géraldine Mathonnet, Marc R. Fabian, Yuri V. Svitkin, Armen Parsyan, Laurent Huck, Takayuki Murata, Stefano Biffo, William C. Merrick, Edward Darzynkiewicz, Ramesh S. Pillai, Witold Filipowicz, Thomas F. Duchaine, Nahum Sonenberg

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368 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) play an important role in gene regulatory networks in animals. Yet, the mechanistic details of their function in translation inhibition or messenger RNA (mRNA) destabilization remain controversial. To directly examine the earliest events in this process, we have developed an in vitro translation system using mouse Krebs-2 ascites cell-free extract that exhibits an authentic miRNA response. We show here that translation initiation, specifically the 5′ cap recognition process, is repressed by endogenous let-7 miRNAs within the first 15 minutes of mRNA exposure to the extract when no destabilization of the transcript is observed. Our results indicate that inhibition of translation initiation is the earliest molecular event effected by miRNAs. Other mechanisms, such as mRNA degradation, may subsequently consolidate mRNA silencing.

Original languageEnglish
Pages (from-to)1764-1767
Number of pages4
JournalScience
Volume317
Issue number5845
DOIs
Publication statusPublished - 21-09-2007

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All Science Journal Classification (ASJC) codes

  • General

Cite this

Mathonnet, G., Fabian, M. R., Svitkin, Y. V., Parsyan, A., Huck, L., Murata, T., Biffo, S., Merrick, W. C., Darzynkiewicz, E., Pillai, R. S., Filipowicz, W., Duchaine, T. F., & Sonenberg, N. (2007). MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science, 317(5845), 1764-1767. https://doi.org/10.1126/science.1146067