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

Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
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;
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.

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.

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.

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