LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs.

• Regulation of mtDNA expression is critical for maintaining cellular energy homeostasis and may, in principle, occur at many different levels. The leucine-rich pentatricopeptide repeat containing (LRPPRC) protein regulates mitochondrial mRNA stability and an amino-acid substitution of this protein causes the French-Canadian type of Leigh syndrome (LSFC), a neurodegenerative disorder characterized by complex IV deficiency. We have generated conditional Lrpprc knockout mice and show here that the gene is essential for embryonic development. Tissue-specific disruption of Lrpprc in heart causes mitochondrial cardiomyopathy with drastic reduction in steady-state levels of most mitochondrial mRNAs. LRPPRC forms an RNA-dependent protein complex that is necessary for maintaining a pool of non-translated mRNAs in mammalian mitochondria. Loss of LRPPRC does not only decrease mRNA stability, but also leads to loss of mRNA polyadenylation and the appearance of aberrant mitochondrial translation. The translation pattern without the presence of LRPPRC is misregulated with excessive translation of some transcripts and no translation of others. Our findings point to the existence of an elaborate machinery that regulates mammalian mtDNA expression at the post-transcriptional level.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Animals

Cytochrome-c Oxidase Deficiency

genetics

DNA

Mitochondrial

genetics

Electron Transport Complex IV

analysis

HeLa Cells

Humans

Leigh Disease

genetics

Macromolecular Substances

Mice

Mice

Knockout

Mitochondria

Heart

physiology

Neoplasm Proteins

deficiency

genetics

physiology

Organ Specificity

Polyadenylation

physiology

Polynucleotide Adenylyltransferase

Protein Biosynthesis

physiology

RNA Stability

RNA

Messenger

RNA-Binding Proteins

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)