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

• Published in: Cell reports (Cambridge) Vol. 31; no. 7; p. 107660
• Main Authors: Nourreddine, Sami, Lavoie, Geneviève, Paradis, Justine, Ben El Kadhi, Khaled, Méant, Antoine, Aubert, Léo, Grondin, Benoit, Gendron, Patrick, Chabot, Benoit, Bouvier, Michel, Carreno, Sébastien, Roux, Philippe P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.05.2020; Elsevier
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107660

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. [Display omitted] •Depletion of NF45 or NF90 leads to pleiotropic mitotic defects•The NF45-NF90 complex associates with, and regulates, a cluster of mitotic mRNAs•The proximity interactome of NF45 and NF90 reveals Stau1 and Stau2•Depletion of Stau1/2 rescues mitotic defects induced by loss of NF45 or NF90 The timely expression of cell cycle genes is finely controlled by specific transcriptional programs. In this study, Nourreddine et al. evaluate the role of RNA-binding proteins in the post-transcriptional regulation of cell cycle genes. They show that the NF45-NF90 complex regulates the expression of an important cluster of mitotic mRNAs.