NF45 and NF90 Regulate Mitotic Gene Expression by Competing with Staufen-Mediated mRNA Decay

Cell Rep. 2020 May 19;31(7):107660. doi: 10.1016/j.celrep.2020.107660.

Sami Nourreddine ¹, Geneviève Lavoie ¹, Justine Paradis ², Khaled Ben El Kadhi ³, Antoine Méant ¹, Léo Aubert ¹, Benoit Grondin ¹, Patrick Gendron ¹, Benoit Chabot ⁴, Michel Bouvier ⁵, Sébastien Carreno ⁶, Philippe P Roux ⁷

Affiliations

1 Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC H3T 1J4, Canada.
2 Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
3 Department of Biology, New York University, New York, NY 10003, USA.
4 Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
5 Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC H3T 1J4, Canada; Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
6 Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC H3T 1J4, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
7 Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC H3T 1J4, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada. Electronic address: [email protected].

PMID: 32433969 DOI: 10.1016/j.celrep.2020.107660

Abstract

In human cells, the expression of ∼1,000 genes is modulated throughout the cell cycle. Although some of these genes are controlled by specific transcriptional programs, very little is known about their post-transcriptional regulation. Here, we analyze the expression signature associated with all 687 RNA-binding proteins (RBPs) and identify 39 that significantly correlate with cell cycle mRNAs. We find that NF45 and NF90 play essential roles in mitosis, and transcriptome analysis reveals that they are necessary for the expression of a subset of mitotic mRNAs. Using proteomics, we identify protein clusters associated with the NF45-NF90 complex, including components of Staufen-mediated mRNA decay (SMD). We show that depletion of SMD components increases the binding of mitotic mRNAs to the NF45-NF90 complex and rescues cells from mitotic defects. Together, our results indicate that the NF45-NF90 complex plays essential roles in mitosis by competing with the SMD machinery for a common set of mRNAs.

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