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

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

Nature communications (2022-06-01)

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

PMID35637192

ANOTACE

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.

MATERIÁLY

Číslo produktu

Značka

Popis produktu

557403

Sigma-Aldrich

RNA Polymerase III Inhibitor, RNA Polymerase III Inhibitor, CAS 577784-91-9, is a cell-permeable inhibitor of RNA Polymerase III (IC₅₀ = 27 and 32 µM for human and S. cerevisiae RNA Pol III, respectively).