POLR2G通过促进XRN2与延长型RNA聚合酶II的结合，从而促进转录终止过程。

Abstract

Acute POLR2G loss reduces Pol II occupancy at promoters and nascent transcription • Acute depletion of POLR2G also causes widespread transcriptional readthrough • POLR2G-associated proteomics recovers XRN2, a transcription-termination factor • POLR2G stabilizes XRN2 association with elongating Pol II at gene 3' ends Transcription termination by RNA polymerase II (Pol II) prevents polymerase readthrough beyond annotated genes and limits transcriptional interference. Although XRN2-mediated RNA degradation is central to the torpedo model of transcription termination, how XRN2 is coupled to elongating Pol II in mammalian cells remains incompletely understood. Here, we used an endogenous AID2-POLR2G depletion system in HepG2 cells to examine the immediate role of the Pol II stalk subunit POLR2G/RPB7. Acute POLR2G depletion reduced promoter-proximal POLR2A occupancy, accompanied by lower nascent transcription across annotated transcription units. Unexpectedly, downstream of transcription end sites, increased POLR2A occupancy coincided with directional nascent transcription. Besides other Pol II subunits, POLR2G-associated proteomics recovered XRN2. Structural analysis of a published Rat1-bound Pol II termination complex, Ser2P Pol II co-immunoprecipitation and XRN2 ChIP-qPCR collectively support a role for POLR2G in promoting XRN2 association with elongating Pol II at gene 3' ends. Re-expression of full-length POLR2G or its XRN2-associated RNA-binding domain reduced readthrough, whereas the N-terminal domain did not. Together, these findings support a model in which POLR2G contributes to efficient transcription termination by facilitating XRN2 association with elongating Pol II. Download: Download high-res image (108KB) Download: Download full-size image