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Article

PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation

1
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
2
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Adrian Harris and Francesco Pezzella
Cells 2021, 10(6), 1425; https://doi.org/10.3390/cells10061425
Received: 13 April 2021 / Revised: 27 May 2021 / Accepted: 4 June 2021 / Published: 8 June 2021
(This article belongs to the Special Issue Hypoxia and Cancer: New Aspects)
PBRM1, a component of the chromatin remodeller SWI/SNF, is often deleted or mutated in human cancers, most prominently in renal cancers. Core components of the SWI/SNF complex have been shown to be important for the cellular response to hypoxia. Here, we investigated how PBRM1 controls HIF-1α activity. We found that PBRM1 is required for HIF-1α transcriptional activity and protein levels. Mechanistically, PBRM1 is important for HIF-1α mRNA translation, as absence of PBRM1 results in reduced actively translating HIF-1α mRNA. Interestingly, we found that PBRM1, but not BRG1, interacts with the m6A reader protein YTHDF2. HIF-1α mRNA is m6A-modified, bound by PBRM1 and YTHDF2. PBRM1 is necessary for YTHDF2 binding to HIF-1α mRNA and reduction of YTHDF2 results in reduced HIF-1α protein expression in cells. Our results identify a SWI/SNF-independent function for PBRM1, interacting with HIF-1α mRNA and the epitranscriptome machinery. Furthermore, our results suggest that the epitranscriptome-associated proteins play a role in the control of hypoxia signalling pathways. View Full-Text
Keywords: PBRM1; HIF-1; SWI/SNF; YTHDF2; m6A; hypoxia PBRM1; HIF-1; SWI/SNF; YTHDF2; m6A; hypoxia
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MDPI and ACS Style

Shmakova, A.; Frost, M.; Batie, M.; Kenneth, N.S.; Rocha, S. PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation. Cells 2021, 10, 1425. https://doi.org/10.3390/cells10061425

AMA Style

Shmakova A, Frost M, Batie M, Kenneth NS, Rocha S. PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation. Cells. 2021; 10(6):1425. https://doi.org/10.3390/cells10061425

Chicago/Turabian Style

Shmakova, Alena, Mark Frost, Michael Batie, Niall S. Kenneth, and Sonia Rocha. 2021. "PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation" Cells 10, no. 6: 1425. https://doi.org/10.3390/cells10061425

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