TY - JOUR
T1 - MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F
AU - Mathonnet, Géraldine
AU - Fabian, Marc R.
AU - Svitkin, Yuri V.
AU - Parsyan, Armen
AU - Huck, Laurent
AU - Murata, Takayuki
AU - Biffo, Stefano
AU - Merrick, William C.
AU - Darzynkiewicz, Edward
AU - Pillai, Ramesh S.
AU - Filipowicz, Witold
AU - Duchaine, Thomas F.
AU - Sonenberg, Nahum
PY - 2007/9/21
Y1 - 2007/9/21
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1146067
DO - 10.1126/science.1146067
M3 - Article
C2 - 17656684
AN - SCOPUS:34547944309
SN - 0036-8075
VL - 317
SP - 1764
EP - 1767
JO - Science
JF - Science
IS - 5845
ER -