生物
RNA诱导沉默复合物
基因沉默
阿尔戈瑙特
RNA沉默
反式siRNA
Piwi相互作用RNA
拉西尔纳
细胞生物学
RNA结合蛋白
重编程
小RNA
RNA干扰
遗传学
核糖核酸
计算生物学
细胞
基因
作者
Thomas Welte,Alison Goulois,Michael Stadler,Daniel Heß,Charlotte Soneson,Anca Neagu,Chiara Azzi,Marlena J. Lübke,J. Seebacher,Isabel Schmidt,David Estoppey,Florian Nigsch,John Reece-Hoyes,Dominic Hoepfner,Helge Großhans
出处
期刊:Molecular Cell
[Elsevier]
日期:2023-06-26
卷期号:83 (14): 2478-2492.e8
被引量:10
标识
DOI:10.1016/j.molcel.2023.06.001
摘要
The RNA-binding protein TRIM71/LIN-41 is a phylogenetically conserved developmental regulator that functions in mammalian stem cell reprogramming, brain development, and cancer. TRIM71 recognizes target mRNAs through hairpin motifs and silences them through molecular mechanisms that await identification. Here, we uncover that TRIM71 represses its targets through RNA-supported interaction with TNRC6/GW182, a core component of the miRNA-induced silencing complex (miRISC). We demonstrate that AGO2, TRIM71, and UPF1 each recruit TNRC6 to specific sets of transcripts to silence them. As cellular TNRC6 levels are limiting, competition occurs among the silencing pathways, such that the loss of AGO proteins or of AGO binding to TNRC6 enhances the activities of the other pathways. We conclude that a miRNA-like silencing activity is shared among different mRNA silencing pathways and that the use of TNRC6 as a central hub provides a means to integrate their activities.
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