Leucine-Rich Pentatricopeptide-Repeat Containing Protein Regulates Mitochondrial Transcription

摘要

Mitochondrial function depends upon the coordinated expression of the mitochondrial andnnuclear genomes. Although the basal factors that carry out the process of mitochondrial transcription arenknown, the regulation of this process is incompletely understood. To further our understanding of mito-nchondrial gene regulation, we identified proteins that bound to the previously described point of terminationnfor the major mRNA-coding transcript H2. One was the leucine-rich pentatricopeptide-repeat containingnprotein (LRPPRC), which has been linked to the French-Canadian variant of Leigh syndrome. Cells withnreduced expression of LRPPRC had a reduction in oxygen consumption. The expression of mitochondrialnmRNA and tRNA was dependent upon LRPPRC levels, but reductions in LRPPRC did not affect thenexpression ofmitochondrial rRNA.Reduction of LRPPRC levels interfered withmitochondrial transcriptionnin vitro but did not affect the stability of mitochondrial mRNAs or alter the expression of nuclear genesnresponsible for mitochondrial transcription in vivo. These findings demonstrate the control of mitochondrialnmRNA synthesis by a protein that has an established role in regulating nuclear transcription and a link tonmitochondrial disease.