Impact of TNRC6 isoforms on gene expression and splicing

Through the RNA interference (RNAi) pathway, small RNAs can influence translation, splicing, transcriptional activation, and transcriptional repression. RNAi is carried out by the targeting Argonaute (Ago) effector protein and the facilitating TNRC6 (also known as GW182) scaffolding protein. Here, we use a suite of gene knockout cell lines and high-throughput sequencing to gather definitive answers about the TNRC6 paralogs, their roles in the cell, and their relation to Ago knockout cell lines. Each subsequent TNRC6 paralog knockout caused more gene changes and few genes overlapped between the single TNRC6 paralog knockouts. In addition, TNRC6 knockout and Ago knockout cell lines’ gene expression profiles are highly correlated with one another, indicating the important regulatory functions these proteins share. Overall we found that in spite of less than 40% sequence identity, TNRC6 paralogs are functionally redundant and can replace one another for core RNAi functions. Total 24 samples, all standard transcriptome-type RNA-seq