An mRNA m7G cap binding-like motif within human Ago2 represses translation

被引：348

作者：

Kiriakidou, Marianthi ^{[1
]}

Tan, Grace S.

Lamprinaki, Styliani

De Planell-Saguer, Mariangels

Nelson, Peter T.

Mourelatos, Zissimos

机构：

[1] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA

来源：

CELL | 2007年 / 129卷 / 06期

关键词：

D O I：

10.1016/j.cell.2007.05.016

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 (miRNAs) bind to Argonaute (Ago) proteins and inhibit translation or promote degradation of mRNA targets. Human let-7 miRNA inhibits translation initiation of mRNA targets in an m(7)G cap-dependent manner and also appears to block protein production, but the molecular mechanism(s) involved is unknown and the role of Ago proteins in translational regulation remains elusive. Here we identify a motif (MC) within the Mid domain of Ago proteins, which bears significant similarity to the m(7)G cap-binding domain of elF4E, an essential translation initiation factor. We identify conserved aromatic residues within the MC motif of human Ago2 that are required for binding to the m(7)G cap and for translational repression but do not affect the assembly of Ago2 with miRNA or its catalytic activity. We propose that Ago2 represses the initiation of mRNA translation by binding to the m(7)G cap of mRNA targets, thus likely precluding the recruitment of elF4E.

引用

页码：1141 / 1151

页数：11

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