Leucine-Rich Pentatricopeptide-Repeat Containing Protein Regulates Mitochondrial Transcription
- 2 August 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 49 (35), 7467-7473
- https://doi.org/10.1021/bi1008479
Abstract
Mitochondrial function depends upon the coordinated expression of the mitochondrial and nuclear genomes. Although the basal factors that carry out the process of mitochondrial transcription are known, the regulation of this process is incompletely understood. To further our understanding of mitochondrial gene regulation, we identified proteins that bound to the previously described point of termination for the major mRNA-coding transcript H2. One was the leucine-rich pentatricopeptide-repeat containing protein (LRPPRC), which has been linked to the French-Canadian variant of Leigh syndrome. Cells with reduced expression of LRPPRC had a reduction in oxygen consumption. The expression of mitochondrial mRNA and tRNA was dependent upon LRPPRC levels, but reductions in LRPPRC did not affect the expression of mitochondrial rRNA. Reduction of LRPPRC levels interfered with mitochondrial transcription in vitro but did not affect the stability of mitochondrial mRNAs or alter the expression of nuclear genes responsible for mitochondrial transcription in vivo. These findings demonstrate the control of mitochondrial mRNA synthesis by a protein that has an established role in regulating nuclear transcription and a link to mitochondrial disease.Keywords
This publication has 40 references indexed in Scilit:
- Coupling the mitochondrial transcription machinery to human diseaseTrends in Genetics, 2004
- 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
- POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletionAnnals of Neurology, 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
- Transcription termination at the mouse mitochondrial H‐strand promoter distal site requires an A/T rich sequence motif and sequence specific DNA binding proteinsEuropean Journal of Biochemistry, 2003
- Activation of the human mitochondrial transcriptionfactor A gene by nuclear respiratory factors: a potential regulatory linkbetween nuclear and mitochondrial gene expression in organellebiogenesis.Proceedings of the National Academy of Sciences, 1994
- A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro.Molecular and Cellular Biology, 1993
- Affinity purification of sequence-specific DNA binding proteins.Proceedings of the National Academy of Sciences, 1986
- The pattern of transcription of the human mitochondrial rRNA genes reveals two overlapping transcription unitsCell, 1983
- Synthesis and turnover of mitochondrial ribonucleic acid in HeLa cells: the mature ribosomal and messenger ribonucleic acid species are metabolically unstable.Molecular and Cellular Biology, 1981