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

MPG-Autoren

Ruzzenente, Benedetta
Max Planck Society;

Metodiev, Metodi D
Max Planck Society;

Wredenberg, Anna
Max Planck Society;

Bratic, Ana
Max Planck Society;

Park, Chan Bae
Max Planck Society;

Camara, Yolanda
Max Planck Society;

Milenkovic, Dusanka
Max Planck Society;

Zickermann, Volker
Max Planck Society;

Wibom, Rolf
Max Planck Society;

Hultenby, Kjell
Max Planck Society;

Erdjument-Bromage, Hediye
Max Planck Society;

Tempst, Paul
Max Planck Society;

Brandt, Ulrich
Max Planck Society;

Stewart, James B
Max Planck Society;

Gustafsson, Claes M
Max Planck Society;

Larsson, Nils-Göran
Max Planck Society;

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Zitation

Ruzzenente, B., Metodiev, M. D., Wredenberg, A., Bratic, A., Park, C. B., Camara, Y., et al. (2012). LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. EMBO J, 31(2), 443-456.

Zusammenfassung

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.