Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice

Tara R. Richman, Henrik Spåhr, Judith A. Ermer, Stefan M. K. Davies, Helena M. Viola, Kristyn A. Bates, John Papadimitriou, Livia C. Hool, Jennifer Rodger, Nils-Göran Larsson, Oliver Rackham and Aleksandra Filipovska ()
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Tara R. Richman: Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia
Henrik Spåhr: Max Planck Institute for Biology of Ageing
Judith A. Ermer: Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia
Stefan M. K. Davies: Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia
Helena M. Viola: School of Anatomy, Physiology and Human Biology, University of Western Australia
Kristyn A. Bates: Experimental and Regenerative Neuroscience, School of Animal Biology, University of Western Australia
John Papadimitriou: School of Pathology and Laboratory Medicine, University of Western Australia
Livia C. Hool: School of Anatomy, Physiology and Human Biology, University of Western Australia
Jennifer Rodger: Experimental and Regenerative Neuroscience, School of Animal Biology, University of Western Australia
Nils-Göran Larsson: Max Planck Institute for Biology of Ageing
Oliver Rackham: Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia
Aleksandra Filipovska: Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract The recognition and translation of mammalian mitochondrial mRNAs are poorly understood. To gain further insights into these processes in vivo, we characterized mice with a missense mutation that causes loss of the translational activator of cytochrome oxidase subunit I (TACO1). We report that TACO1 is not required for embryonic survival, although the mutant mice have substantially reduced COXI protein, causing an isolated complex IV deficiency. We show that TACO1 specifically binds the mt-Co1 mRNA and is required for translation of COXI through its association with the mitochondrial ribosome. We determined the atomic structure of TACO1, revealing three domains in the shape of a hook with a tunnel between domains 1 and 3. Mutations in the positively charged domain 1 reduce RNA binding by TACO1. The Taco1 mutant mice develop a late-onset visual impairment, motor dysfunction and cardiac hypertrophy and thus provide a useful model for future treatment trials for mitochondrial disease.

Date: 2016
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DOI: 10.1038/ncomms11884

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