Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9

Elife. 2017 Feb 21;6:e18825. doi: 10.7554/eLife.18825.

Abstract

Beyond their role at nuclear pore complexes, some nucleoporins function in the nucleoplasm. One such nucleoporin, Nup98, binds chromatin and regulates gene expression. To gain insight into how Nup98 contributes to this process, we focused on identifying novel binding partners and understanding the significance of these interactions. Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner. Importantly, binding of Nup98 stimulates the ATPase activity of DHX9, and a transcriptional reporter assay suggests Nup98 supports DHX9-stimulated transcription. Consistent with these observations, our analysis revealed that Nup98 and DHX9 bind interdependently to similar gene loci and their transcripts. Based on our results, we propose that Nup98 functions as a co-factor that regulates DHX9 and, potentially, other RNA helicases.

Keywords: DExH/D-box helicase; DHX9; Nup98; RNA helicase A; cell biology; gene expression and mRNA metabolism; human; nuclear pore complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DEAD-box RNA Helicases / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Neoplasm Proteins / metabolism*
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Transport
  • RNA / metabolism

Substances

  • Neoplasm Proteins
  • Nuclear Pore Complex Proteins
  • Nup98 protein, human
  • RNA
  • DHX9 protein, human
  • DEAD-box RNA Helicases

Grant support