A Cancer-associated RNA Polymerase III Identity Drives Robust Transcription and Expression of SnaR-A Noncoding RNA

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 31

PMID 35637192

Authors

Kevin Van Bortle

David P Marciano

Qing Liu

Tristan Chou

Andrew M Lipchik

Sanjay Gollapudi

Benjamin S Geller

Emma Monte

Rohinton T Kamakaka

Michael P Snyder

Affiliations

Soon will be listed here.

Abstract

RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7α) or POLR3GL (RPC7β), in mammals. The contributions of POLR3G and POLR3GL to transcription potential has remained poorly defined. Here, we discover that loss of subunit POLR3G is accompanied by a restricted repertoire of genes transcribed by Pol III. Particularly sensitive is snaR-A, a small noncoding RNA implicated in cancer proliferation and metastasis. Analysis of Pol III isoform biases and downstream chromatin features identifies loss of POLR3G and snaR-A during differentiation, and conversely, re-establishment of POLR3G gene expression and SNAR-A gene features in cancer contexts. Our results support a model in which Pol III identity functions as an important transcriptional regulatory mechanism. Upregulation of POLR3G, which is driven by MYC, identifies a subgroup of patients with unfavorable survival outcomes in specific cancers, further implicating the POLR3G-enhanced transcription repertoire as a potential disease factor.

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