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

Author

Listed:
  • Kevin Van Bortle

    (Stanford University
    University of Illinois Urbana-Champaign
    University of Illinois Urbana-Champaign)

  • David P. Marciano

    (Stanford University)

  • Qing Liu

    (Stanford University
    Stanford University School of Medicine
    Southern Illinois University School of Medicine)

  • Tristan Chou

    (Stanford University)

  • Andrew M. Lipchik

    (Stanford University
    Wayne State University)

  • Sanjay Gollapudi

    (Stanford University)

  • Benjamin S. Geller

    (Stanford University
    University of Santa Cruz)

  • Emma Monte

    (Stanford University)

  • Rohinton T. Kamakaka

    (University of Santa Cruz)

  • Michael P. Snyder

    (Stanford University)

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.

Suggested Citation

  • 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, 2022. "A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30323-6
    DOI: 10.1038/s41467-022-30323-6
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    References listed on IDEAS

    as
    1. Guillermo Abascal-Palacios & Ewan Phillip Ramsay & Fabienne Beuron & Edward Morris & Alessandro Vannini, 2018. "Structural basis of RNA polymerase III transcription initiation," Nature, Nature, vol. 553(7688), pages 301-306, January.
    2. Niklas A. Hoffmann & Arjen J. Jakobi & María Moreno-Morcillo & Sebastian Glatt & Jan Kosinski & Wim J. H. Hagen & Carsten Sachse & Christoph W. Müller, 2015. "Molecular structures of unbound and transcribing RNA polymerase III," Nature, Nature, vol. 528(7581), pages 231-236, December.
    Full references (including those not matched with items on IDEAS)

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