Asymmetry in the assembly of the RNAi enzyme complex (Reprinted from Cell, vol 115, pg 199-208, 2003)

被引：1953

作者：

Schwarz, Dianne S. ^{[1
]}

Hutvagner, Gyoergy ^{[1
,2
]}

Du, Tingting ^{[1
]}

Xu, Zuoshang ^{[1
]}

Aronin, Neil ^{[2
]}

Zamore, Phillip D. ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA

[2] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA

来源：

CELL | 2007年 / 131卷 / 04期

基金：

美国国家卫生研究院;

关键词：

DOUBLE-STRANDED-RNA; SHORT-INTERFERING RNAS; MESSENGER-RNA; GENE-EXPRESSION; HAIRPIN RNAS; C-ELEGANS; DROSOPHILA; SIRNAS; DICER; MICRORNAS;

D O I：

10.1016/S0092-8674(03)00759-1

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：

A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5' ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis.

引用

页码：30 / 40

页数：11

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