miRNA-Mediated Gene Silencing by Translational Repression Followed by mRNA Deadenylation and Decay

被引:638
作者
Djuranovic, Sergej
Nahvi, Ali
Green, Rachel [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst HHMI, Baltimore, MD 21205 USA
关键词
POLY(A) TAIL; MAMMALIAN-CELLS; GW182; PROTEINS; LET-7; MICRORNA; INITIATION; CAP; CCR4-NOT; TARGETS; DEGRADATION; INHIBITION;
D O I
10.1126/science.1215691
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:237 / 240
页数:5
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