TNRC6 is a scaffolding protein that bridges interactions between small RNAs, argonaute (AGO) protein, and effector proteins to control gene expression. There are three paralogs in mammalian cells, TNRC6A, TNRC6B, and TNRC6C. These paralogs have ∼40% amino acid sequence identity and the extent of their unique or redundant functions is unclear. Here, we use knockout cell lines, enhanced crosslinking immunoprecipitation (eCLIP), and high-throughput RNA sequencing (RNA-seq) to explore the roles of TNRC6 paralogs in RNA-mediated control of gene expression. We find that the paralogs are largely functionally redundant and changes in levels of gene expression are well-correlated with those observed in AGO knockout cell lines. Splicing changes observed in AGO knockout cell lines are also observed in TNRC6 knockout cells. These data further define the roles of the TNRC6 isoforms as part of the RNA interference (RNAi) machinery.

中文翻译：

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支架蛋白 TNRC6 旁系同源物对基因表达和剪接的影响

TNRC6 是一种支架蛋白，可桥接小 RNA、argonaute (AGO) 蛋白和效应蛋白之间的相互作用以控制基因表达。哺乳动物细胞中存在三个旁系同源物，TNRC6A、TNRC6B和TNRC6C。这些旁系同源物具有约 40% 的氨基酸序列同一性，其独特或冗余功能的程度尚不清楚。在这里，我们使用敲除细胞系、增强交联免疫沉淀 (eCLIP) 和高通量 RNA 测序 (RNA-seq) 来探索 TNRC6 旁系同源物在 RNA 介导的基因表达控制中的作用。我们发现旁系同源物在很大程度上是功能冗余的，基因表达水平的变化与AGO中观察到的变化密切相关敲除细胞系。在AGO敲除细胞系中观察到的剪接变化也在TNRC6敲除细胞中观察到。这些数据进一步定义了 TNRC6 亚型作为 RNA 干扰 (RNAi) 机制的一部分的作用。