A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA

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

doi:10.1038/s41467-022-30323-6

A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA

Nat Commun. 2022 May 30;13(1):3007. doi: 10.1038/s41467-022-30323-6.

Authors

Kevin Van Bortle^{1

2

3}, David P Marciano¹, Qing Liu^{1

4

5}, Tristan Chou¹, Andrew M Lipchik^{1

6}, Sanjay Gollapudi⁷, Benjamin S Geller^{1

8}, Emma Monte¹, Rohinton T Kamakaka⁸, Michael P Snyder⁹

Affiliations

¹ Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
² Department of Cell & Developmental Biology, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
³ Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
⁴ Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.
⁵ Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, 62901, USA.
⁶ Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, 48201, USA.
⁷ Genomics Research Internship Program at Stanford, Stanford University, Stanford, CA, 94305, USA.
⁸ Department of Molecular, Cell, and Developmental Biology, University of Santa Cruz, Santa Cruz, CA, 95064, USA.
⁹ Department of Genetics, Stanford University, Stanford, CA, 94305, USA. mpsnyder@stanford.edu.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Chromatin
Humans
Mammals / genetics
Neoplasms* / genetics
Protein Isoforms / genetics
RNA Polymerase III / genetics
RNA Polymerase III / metabolism
RNA, Small Untranslated*

Substances

Chromatin
Protein Isoforms
RNA, Small Untranslated
POLR3G protein, human
RNA Polymerase III

Abstract

Publication types

MeSH terms

Substances

Grants and funding