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Nucleic Acids Research Advance Access originally published online on August 3, 2009
Nucleic Acids Research 2009 37(17):5859-5867; doi:10.1093/nar/gkp627
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Nucleic Acids Research, 2009, Vol. 37, No. 17 5859-5867
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

Pentatricopeptide repeat domain protein 1 lowers the levels of mitochondrial leucine tRNAs in cells

Oliver Rackham1, Stefan M. K. Davies1, Anne-Marie J. Shearwood1, Kristina L. Hamilton1, James Whelan2 and Aleksandra Filipovska1,*

1Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, WA 6000 and 2Australian Research Council Centre of Excellence in Plant Energy Biology, The University of Western Australia, Crawley, WA 6009, Australia

*To whom correspondence should be addressed. Tel: +61 8 9224 0330; Fax: +61 8 9224 0322; Email: afilipov{at}waimr.uwa.edu.au

Received February 24, 2009. Revised June 27, 2009. Accepted July 14, 2009.

Although the basic components and mechanisms of mitochondrial transcription in mammals have been described, the components involved in mRNA processing, translation and stability remain largely unknown. In plants, pentatricopeptide domain RNA-binding proteins regulate the stability, expression and translation of mitochondrial transcripts; therefore, we investigated the role of an uncharacterized mammalian pentatricopeptide domain protein, (PTCD1), in mitochondrial RNA metabolism. We show that PTCD1 is a mitochondrial matrix protein which associates with leucine tRNAs and precursor RNAs that contain leucine tRNAs. Knockdown of PTCD1 in 143B osteosarcoma cells did not change mitochondrial mRNA levels; however, it increased the abundance precursor RNAs and of leucine tRNAs and PTCD1 overexpression led to a reduction of these RNAs. Lowering PTCD1 in cells increased levels of several mitochondria-encoded proteins and Complex IV activity, suggesting that PTCD1 acts as a negative regulator of leucine tRNA levels and hence mitochondrial translation.


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