Human GW182 Paralogs Are the Central Organizers for RNA-Mediated Control of Transcription

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Jessica A. Hicks, Liande Li, Masayuki Matsui, Yongjun Chu, Oleg Volkov, Krystal C. Johnson, David R. Corey
In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and investigation of its natural regulatory roles. Here, we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone-modifying complexes. Functional analysis implicates TNRC6A, NAT10, MED14, and WDR5 in RNA-mediated transcriptional activation. These findings describe protein complexes capable of bridging RNA-mediated sequence-specific recognition of noncoding RNA transcripts with the regulation of gene transcription.

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Teaser

Nuclear RNAi has the potential to add a previously unrecognized layer of control over mammalian gene expression. Hicks et al. use mass spectrometry to expand identification of protein partners that may play roles in RNA-mediated regulation of transcription and splicing.


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