Shmakova, Alena, Frost, Mark, Kenneth, Niall and Rocha, Sonia 
ORCID: 0000-0002-2413-4981
(2021)
PBRM1 Cooperates with YTHDF2 to Control HIF-1Alpha Protein Translation.
Cells.
202104.0359.v1-.
Abstract
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-1alpha activity. We find that PBRM1 is required for HIF-1alpha transcriptional activity and protein levels. Mechanistically, PBRM1 is important for HIF-1alpha mRNA translation, as absence of PBRM1 results in reduced activly transalting HIF-1alpha mRNA. Interestingly, we find that PBRM1, but not BRG1, interacts with the m6A reader protein YTHDF2. HIF-1alpha mRNA is m6A modified, bound by PBRM1 and YTHDF2. PBRM1 is necessary for YTHDF2 binding to HIF-1alpha mRNA and reduction of YTHDF2 results in reduced HIF-1alpha protein expression in cells. Our results identify a SWI/SNF independent function for PBRM1, interacting with HIF-1alpha mRNA and the epitranscriptome machinery. Furthermore, our results suggests that the epitranscriptome associated proteins play a role in the control of hypoxia signalling pathways
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Genetics, 1 Underpinning research, 1.1 Normal biological development and functioning, 3 Good Health and Well Being |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 05 Apr 2022 14:25 |
| Last Modified: | 15 Mar 2024 16:23 |
| DOI: | 10.20944/preprints202104.0359.v1 |
| Open Access URL: | https://www.mdpi.com/2073-4409/10/6/1425 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3152172 |
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