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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Gene Expression Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mitosis / genetics
  • Mitosis / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Factor 45 Protein / genetics
  • Nuclear Factor 45 Protein / metabolism*
  • Nuclear Factor 90 Proteins / genetics
  • Nuclear Factor 90 Proteins / metabolism*
  • RNA Stability / genetics
  • RNA Stability / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • Cytoskeletal Proteins
  • ILF2 protein, human
  • ILF3 protein, human
  • Nerve Tissue Proteins
  • Nuclear Factor 45 Protein
  • Nuclear Factor 90 Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • STAU1 protein, human
  • STAU2 protein, human