biostudies-literatureJohnson STthe Robert Welch FoundationNEI NIH HHSNational Institutes of HealthRusty Kelley Professorship in Medical ScienceNIH predoctoral fellowshipNIGMS NIH HHS1004-1016https://www.ebi.ac.uk/biostudies/studies/S-EPMC8370741biostudies-literatureUnknown27(9)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, <i>TNRC6A</i>, <i>TNRC6B</i>, and <i>TNRC6C</i> 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 <i>AGO</i> knockout cell lines. Splicing changes observed in <i>AGO</i> knockout cell lines are also observed in <i>TNRC6</i> knockout cells. These data further define the roles of the TNRC6 isoforms as part of the RNA interference (RNAi) machinery.RNA (New York, N.Y.)Impact of scaffolding protein TNRC6 paralogs on gene expression and splicing.PMC8370741F31 EY030336GM106151I-1244R35 GM1181035 F31 EY030336-03R01 GM106151Johnson STLiu JCorey DRChu YfalseImpact of scaffolding protein TNRC6 paralogs on gene expression and splicing.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, <i>TNRC6A</i>, <i>TNRC6B</i>, and <i>TNRC6C</i> 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 <i>AGO</i> knockout cell lines. Splicing changes observed in <i>AGO</i> knockout cell lines are also observed in <i>TNRC6</i> knockout cells. These data further define the roles of the TNRC6 isoforms as part of the RNA interference (RNAi) machinery.2021-01-01T00:00:00Z2021 Sep2024-11-05T22:40:19.17Z2022-02-11T10:05:39.015ZS-EPMC83707413410823110.1261/rna.078709.121