The P-body component USP52/PAN2 is a novel regulator of HIF1A mRNA stability

Hypoxia Inducible Factor-1 alpha (HIF1A) is the master regulator of the cellular response to hypoxia and is implicated in cancer progression. While the regulation of HIF1A protein in response to oxygen is well characterized, less is known about the fate of HIF1A mRNA. Here, we have identified the pseudoDUB/deadenylase USP52/PAN2 as an important regulator of the HIF1A-mediated hypoxic response. Depletion of USP52 reduced HIF1A mRNA and protein levels and resulted in reduced expression of HIF1A-regulated hypoxic targets due to a 3’UTR-dependent, polyA-tail length-independent destabilization in HIF1A mRNA. Mass spectrometry analysis revealed an association of USP52 with several P-body components and we further confirmed that USP52 protein and HIF1A mRNA co-localized with cytoplasmic P-bodies. Importantly, P-body dispersal by knockdown of GW182 or LSM1 resulted in a reduction of HIF1A mRNA levels. These data uncover a novel role for P-bodies in regulating HIF1A mRNA stability, and demonstrate that USP52 is a key component of P-bodies required to prevent HIF1A mRNA degradation.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research