HuR controls mitochondrial morphology through the regulation of BclxL translation

Danielle Durie; Maria Hatzoglou; Pranesh Chakraborty; Martin Holcik

doi:10.4161/trla.23980

HuR controls mitochondrial morphology through the regulation of Bcl_xL translation

Translation (Austin). 2013 Apr 1;1(1):e23980. doi: 10.4161/trla.23980.

Authors

Danielle Durie¹, Maria Hatzoglou², Pranesh Chakraborty³, Martin Holcik⁴

Affiliations

¹ Apoptosis Research Center, Children's Hospital of Eastern Ontario Research Institute.
² Department of Nutrition, Case Western Reserve University, School of Medicine, Cleveland, Ohio, U.S.A.
³ Department of Pediatrics, University of Ottawa ; Newborn Screening Ontario, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, K1H 8L1, Canada.
⁴ Apoptosis Research Center, Children's Hospital of Eastern Ontario Research Institute ; Department of Pediatrics, University of Ottawa.

Abstract

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.

Keywords: IRES; ITAF; RNA binding protein; mitochondrial dynamics; translational control.

Abstract

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