Rxivist logo

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

By Kevin Van Bortle, David P Marciano, Qing Liu, Andrew M. Lipchik, Sanjay Gollapudi, Benjamin S Geller, Emma Monte, Rohinton T Kamakaka, Michael Snyder

Posted 22 Apr 2021
bioRxiv DOI: 10.1101/2021.04.21.440535

Dysregulation of the RNA polymerase III (Pol III) transcription program, which synthesizes tRNA and other classes of small noncoding RNA critical for cell growth and proliferation, is associated with cancer and human disease. Previous studies have identified two distinct Pol III isoforms defined by the incorporation of either subunit POLR3G (RPC7) during early development, or POLR3GL (RPC7{beta}) in specialized tissues. Though POLR3G is re-established in cancer and immortalized cell lines, the contributions of these isoforms to transcription potential and transcription dysregulation in cancer remain poorly defined. Using an integrated Pol III genomic profiling approach in combination with in vitro differentiation and subunit disruption experiments, we discover that loss of subunit POLR3G is accompanied by a restricted repertoire of genes transcribed by Pol III. In particular, we observe that a specific class of small noncoding RNA, SNAR-A, is exquisitely sensitive to the availability of subunit POLR3G in proliferating cells. Taken further, large-scale analysis of Pol III subunit expression and downstream chromatin features identifies concomitant loss of POLR3G and SNAR-A activity across a multitude of differentiated primary immune cell lineages, and conversely, coordinate re-establishment of POLR3G expression and SNAR-A features in a variety of human cancers. These results altogether argue against strict redundancy models for subunits POLR3G and POLR3GL, and instead support a model in which Pol III identity itself 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.

Download data

  • Downloaded 561 times
  • Download rankings, all-time:
    • Site-wide: 66,375
    • In molecular biology: 1,892
  • Year to date:
    • Site-wide: 33,846
  • Since beginning of last month:
    • Site-wide: 29,742

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide