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Nucleic Acids Res. 2017 Dec 1;45(21):12509-12528. doi: 10.1093/nar/gkx963.

Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA metabolism.

Author information

1
Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec H2W 1R7, Canada.
2
Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 1A3, Canada.
3
Département de Biochimie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
4
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
5
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Molecular Engineering Laboratory, A*STAR, Singapore.

Abstract

To counteract the breakdown of genome integrity, eukaryotic cells have developed a network of surveillance pathways to prevent and resolve DNA damage. Recent data has recognized the importance of RNA binding proteins (RBPs) in DNA damage repair (DDR) pathways. Here, we describe Nol12 as a multifunctional RBP with roles in RNA metabolism and genome maintenance. Nol12 is found in different subcellular compartments-nucleoli, where it associates with ribosomal RNA and is required for efficient separation of large and small subunit precursors at site 2; the nucleoplasm, where it co-localizes with the RNA/DNA helicase Dhx9 and paraspeckles; as well as GW/P-bodies in the cytoplasm. Loss of Nol12 results in the inability of cells to recover from DNA stress and a rapid p53-independent ATR-Chk1-mediated apoptotic response. Nol12 co-localizes with DNA repair proteins in vivo including Dhx9, as well as with TOPBP1 at sites of replication stalls, suggesting a role for Nol12 in the resolution of DNA stress and maintenance of genome integrity. Identification of a complex Nol12 interactome, which includes NONO, Dhx9, DNA-PK and Stau1, further supports the protein's diverse functions in RNA metabolism and DNA maintenance, establishing Nol12 as a multifunctional RBP essential for genome integrity.

PMID:
29069457
DOI:
10.1093/nar/gkx963
[Indexed for MEDLINE]

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