HuR controls mitochondrial morphology through the regulation of Bcl_xL translation

Bcl_xL is a key prosurvival factor that in addition to controlling mitochondrial membrane permeability regulates mitochondrial network dynamics. The expression of Bcl_xL 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 Bcl_xL. We show that HuR binds directly to the 5'UTR of Bcl_xL, and represses Bcl_xL translation through the inhibition of its internal ribosome entry site (IRES). Reduction of HuR levels leads to the derepression of Bcl_xL translation and subsequent rearrangement of the mitochondrial network. Our results place Bcl_xL into the HuR-regulated operon and provide further insight into the regulation of cellular stress response by HuR.