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TRBP将Dicer复合体招募到Ago2进行微RNA处理和基因沉默

Thimmaiah P Chendrimada¹, Richard I Gregory, Easwari Kumaraswamy

¹The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.

|June 24, 2005

概括

TRBP蛋白对于微RNA (miRNA) 生物发生和RNA诱导的沉默复合体 (RISC) 组合至关重要. 它稳定了Dicer,招募了Argonaute 2 (Ago2),并促进了基因沉默.

科学领域:

分子生物学分子生物学
在RNA生物学,RNA生物学.
基因规则基因规则

背景情况:

微RNAs (miRNAs) 是基因表达在转录后水平的关键调节者.
miRNA生物生成涉及微处理器复合体和Dicer.的两步处理途径.
RNA诱导的沉默复合体 (RISC) 通过准互补的信使RNA来调解基因沉默.

研究的目的:

研究TRBP (交互激活响应RNA结合蛋白) 在miRNA生物发生和RISC组装中的作用.
为了阐明TRBP,Dicer和Argonaute 2 (Ago2) 之间的相互作用.

主要方法:

含有TRBP复合物的生物化学分析.
使用Flag标记的Ago2细胞系隔离三元复合体.
在体外复制试验和siRNA介导的淘汰试验.

主要成果:

TRBP是Dicer含有复合物的组成部分,与Ago2结合在一起.
对于Ago2对Dicer.结合的小干扰RNA (siRNA) 的招募,TRBP是必要的.
通过TRBP敲击破坏Dicer的稳定,导致miRNA生物发生率降低和RISC介导的基因沉默.

结论:

在miRNA处理和RISC组装中,Dicer-TRBP复合体起着至关重要的作用.
TRBP作为RISC组装的平台,对于高效的基因沉默至关重要.

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