HuR controls mitochondrial morphology through the regulation of Bcl xL translation

Abstract

BclxL is a key prosurvival factor that in addition to controlling mitochondrial membrane permeability regulates mitochondrial network dynamics. The expression of BclxL is regulated at the level of translation, splicing and selective translation. In this study, we show that the RNA-binding protein HuR, which is known to orchestrate an anti-apoptotic cellular program, functions as a translational repressor of BclxL. We show that HuR binds directly to the 5'UTR of BclxL, and represses BclxL translation through the inhibition of its internal ribosome entry site (IRES). Reduction of HuR levels leads to the derepression of BclxL translation and subsequent rearrangement of the mitochondrial network. Our results place BclxL into the HuR-regulated operon and provide further insight into the regulation of cellular stress response by HuR.