Alternative translation initiation augments the human mitochondrial proteome

Kazak, L., Reyes, A., Duncan, A. L., Rorbach, J., Wood, S. R., Brea-Calvo, G., Gammage, P. A. , Robinson, A. J., Minczuk, M. and Holt, I. J. (2013) Alternative translation initiation augments the human mitochondrial proteome. Nucleic Acids Research, 41(4), pp. 2354-2369. (doi: 10.1093/nar/gks1347) (PMID:23275553) (PMCID:PMC3575844)

211824.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.



Alternative translation initiation (ATI) is a mechanism of producing multiple proteins from a single transcript, which in some cases regulates trafficking of proteins to different cellular compartments, including mitochondria. Application of a genome-wide computational screen predicts a cryptic mitochondrial targeting signal for 126 proteins in mouse and man that is revealed when an AUG codon located downstream from the canonical initiator methionine codon is used as a translation start site, which we term downstream ATI (dATI). Experimental evidence in support of dATI is provided by immunoblotting of endogenous truncated proteins enriched in mitochondrial cell fractions or of co-localization with mitochondria using immunocytochemistry. More detailed cellular localization studies establish mitochondrial targeting of a member of the cytosolic poly(A) binding protein family, PABPC5, and of the RNA/DNA helicase PIF1α. The mitochondrial isoform of PABPC5 co-immunoprecipitates with the mitochondrial poly(A) polymerase, and is markedly reduced in abundance when mitochondrial DNA and RNA are depleted, suggesting it plays a role in RNA metabolism in the organelle. Like PABPC5 and PIF1α, most of the candidates identified by the screen are not currently annotated as mitochondrial proteins, and so dATI expands the human mitochondrial proteome.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Gammage, Dr Payam
Authors: Kazak, L., Reyes, A., Duncan, A. L., Rorbach, J., Wood, S. R., Brea-Calvo, G., Gammage, P. A., Robinson, A. J., Minczuk, M., and Holt, I. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nucleic Acids Research
Publisher:Oxford University Press
ISSN (Online):1362-4962
Published Online:25 December 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in Nucleic Acids Research 41(4):2354-2369
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record