Pentatricopeptide repeat domain protein 1 lowers the levels of mitochondrial leucine tRNAs in cells.
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.
Rackham
Oliver
O
Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, WA 6000, Australia.
Davies
Stefan M K
SM
Shearwood
Anne-Marie J
AM
Hamilton
Kristina L
KL
Whelan
James
J
Filipovska
Aleksandra
A
D045744:Cell Line, Tumor; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D045222:Electron Transport Chain Complex Proteins; D024101:Mitochondrial Proteins; C544933:PTCD1 protein, human; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu; D016601:RNA-Binding Proteins; D012313:RNA