Abstract：
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.
摘要：
RNA结合蛋白TRIM71/LIN-41是一种系统发育保守的发育调节因子，在哺乳动物干细胞重编程中起作用，大脑发育,和癌症。TRIM71通过发夹基序识别靶mRNA，并通过等待鉴定的分子机制沉默它们。这里,我们发现TRIM71通过RNA支持的与miRNA诱导的沉默复合物(miRISC)的核心成分TNRC6/GW182的相互作用抑制其靶标.我们证明了AGO2，TRIM71和UPF1各自招募TNRC6到特定的转录本组以使它们沉默。由于细胞TNRC6水平有限，竞争发生在沉默途径之间，这样AGO蛋白或AGO与TNRC6结合的丧失增强了其他途径的活性。我们得出结论，miRNA样沉默活性在不同的mRNA沉默途径中共享，并且使用TNRC6作为中心枢纽提供了整合其活性的手段。
