Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9
- University of Alberta, Canada
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.
Data availability
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DamID in HeLa-C cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE83692).
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Widespread RNA Binding by Chromatin Associated ProteinsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE67963).
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RNA-seq in HepG2 and IMR90 cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE83551).
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RNA helicase A is necessary for KIF1Bβ tumor suppression in neuroblastomaPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE44585).
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Supplementary Table 1Publicly available at the NCBI PubMed Central (PMCID: PMC4333382).
Article and author information
Author details
Funding
Alberta Innovates - Health Solutions (Graduate Studentship)
- Juliana S Capitanio
Canadian Institutes of Health Research (MRC Operating Grant Program,130231)
- Ben Montpetit
Canadian Institutes of Health Research (MRC Operating Grant Program,106502 and 36519)
- Richard W Wozniak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Karsten Weis, ETH Zurich, Switzerland
Version history
- Received: June 15, 2016
- Accepted: February 16, 2017
- Accepted Manuscript published: February 21, 2017 (version 1)
- Version of Record published: March 6, 2017 (version 2)
Copyright
© 2017, Capitanio et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9
eLife 6:e18825.
https://doi.org/10.7554/eLife.18825
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