Drosophila Argonaute1 and Argonaute2 Employ Distinct Mechanisms for Translational Repression

被引:147
作者
Iwasaki, Shintaro [1 ,2 ]
Kawamata, Tomoko [1 ]
Tomari, Yukihide [1 ,2 ,3 ]
机构
[1] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan
[2] Univ Tokyo, Dept Med Genome Sci, Bunkyo Ku, Tokyo 1130032, Japan
[3] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
关键词
MESSENGER-RNA DEADENYLATION; CAP-DEPENDENT TRANSLATION; INITIATION-FACTOR; ENDOGENOUS SIRNAS; GENE-EXPRESSION; LET-7; MICRORNA; CAF1; PROTEINS; IN-VITRO; INTERFERENCE; COMPLEX;
D O I
10.1016/j.molcel.2009.02.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
microRNAs induce translational repression by binding to partially complementary sites on their target mRNAs. We have established an in vitro system that recapitulates translational repression mediated by the two Drosophila Argonaute (Ago) subfamily proteins, Ago1 and Ago2. We find that Ago1-RISC (RNA-induced silencing complex) represses translation primarily by ATP-dependent shortening of the poly(A) tail of its mRNA targets. Ago1-RISC can also secondarily block a step after cap recognition. In contrast, Ago2-RISC competitively blocks the interaction of elF4E with elF4G and inhibits the cap function. Our finding that the two Ago proteins in flies regulate translation by different mechanisms may reconcile previous, contradictory explanations for how miRNAs repress protein synthesis.
引用
收藏
页码:58 / 67
页数:10
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