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Nol12 is a multifunctional endonuclease at the nexus of RNA and DNA metabolism

D. D. Scott, C. Trahan, P.J. Zindy, L.C. Aguilar, M.Y. Delubac, K. E. Wei, M. Oeffinger
doi: https://doi.org/10.1101/043935
D. D. Scott
1Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada, H2W 1R7;
2Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada H3A 1A3;
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C. Trahan
1Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada, H2W 1R7;
3Département de Biochimie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3T 1J4;
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P.J. Zindy
1Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada, H2W 1R7;
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L.C. Aguilar
1Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada, H2W 1R7;
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M.Y. Delubac
1Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada, H2W 1R7;
3Département de Biochimie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3T 1J4;
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K. E. Wei
1Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada, H2W 1R7;
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M. Oeffinger
1Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada, H2W 1R7;
2Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada H3A 1A3;
3Département de Biochimie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3T 1J4;
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  • For correspondence: marlene.oeffinger@ircm.qc.ca
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ABSTRACT

Endo‐ and exonucleases are major contributors to RNA metabolism through their diverse roles in maturation and turnover of different species of RNA as well as transcription. Recent data suggests RNA nucleases also affect genome stability programs and act along DNA repair pathways. Here, we describe Nol12 as a multifunctional RNA/DNA endonuclease found in different subcellular compartments - the nucleoplasm, where it co-localizes with the RNA/DNA helicase Dhx9 and paraspeckles, nucleoli as well as GW/P-bodies. We show that Nol12 is required for a key step in ribosomal RNA processing, separating large and small subunit precursors at site 2, rerouting ribosome biogenesis via an alternative pathway in its absence to ensure ribosome production. Furthermore, loss of Nol12 results in increased oxidized DNA levels followed by a rapid p53-independent ATR-Chk1-mediated apoptotic response, suggesting a role for Nol12 in the prevention or resolution of oxidative DNA damage. Identification of a complex Nol12 interactome, which includes NONO, Dhx9 and DNA-PK, further supports its diverse functions in RNA metabolism and DNA maintenance, establishing Nol12 as a multifunctional endonuclease.

Footnotes

  • ↵† The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 16, 2016.
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Nol12 is a multifunctional endonuclease at the nexus of RNA and DNA metabolism
D. D. Scott, C. Trahan, P.J. Zindy, L.C. Aguilar, M.Y. Delubac, K. E. Wei, M. Oeffinger
bioRxiv 043935; doi: https://doi.org/10.1101/043935
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Nol12 is a multifunctional endonuclease at the nexus of RNA and DNA metabolism
D. D. Scott, C. Trahan, P.J. Zindy, L.C. Aguilar, M.Y. Delubac, K. E. Wei, M. Oeffinger
bioRxiv 043935; doi: https://doi.org/10.1101/043935

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