Pentatricopeptide repeat domain protein 1 lowers the levels of mitochondrial leucine tRNAs in cells
Open Access
- 3 August 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 37 (17), 5859-5867
- https://doi.org/10.1093/nar/gkp627
Abstract
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.Keywords
This publication has 31 references indexed in Scilit:
- Pentatricopeptide repeat domain protein 3 associates with the mitochondrial small ribosomal subunit and regulates translationFEBS Letters, 2009
- RNase P without RNA: Identification and Functional Reconstitution of the Human Mitochondrial tRNA Processing EnzymeCell, 2008
- tRNA cleavage is a conserved response to oxidative stress in eukaryotesRNA, 2008
- Developmentally regulated cleavage of tRNAs in the bacterium Streptomyces coelicolorNucleic Acids Research, 2007
- A gold(I) phosphine complex selectively induces apoptosis in breast cancer cells: Implications for anticancer therapeutics targeted to mitochondriaBiochemical Pharmacology, 2007
- A large-scale screening of the normalized mammalian mitochondrial gene expression profilesGenetics Research, 2005
- Mitochondrial DNA mutations in human diseaseNature Reviews Genetics, 2005
- The role of the LRPPRC (leucine-rich pentatricopeptide repeat cassette) gene in cytochrome oxidase assembly: mutation causes lowered levels of COX (cytochrome c oxidase) I and COX III mRNABiochemical Journal, 2004
- Messenger RNA stability in mitochondria: different means to an endTrends in Genetics, 2004
- LRP130, a Pentatricopeptide Motif Protein with a Noncanonical RNA-Binding Domain, Is Bound In Vivo to Mitochondrial and Nuclear RNAsMolecular and Cellular Biology, 2003