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Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly.

MPG-Autoren

Rackham,  Oliver
Max Planck Institute for Biology of Ageing, Max Planck Society;

Busch,  Jakob D
Max Planck Institute for Biology of Ageing, Max Planck Society;

Matic,  Stanka
Max Planck Institute for Biology of Ageing, Max Planck Society;

Siira,  Stefan J
Max Planck Institute for Biology of Ageing, Max Planck Society;

Kuznetsova,  Irina
Max Planck Institute for Biology of Ageing, Max Planck Society;

Atanassov,  Ilian
Max Planck Institute for Biology of Ageing, Max Planck Society;

Ermer,  Judith A
Max Planck Institute for Biology of Ageing, Max Planck Society;

Shearwood,  Anne-Marie J
Max Planck Institute for Biology of Ageing, Max Planck Society;

Richman,  Tara R
Max Planck Institute for Biology of Ageing, Max Planck Society;

Stewart,  James B
Max Planck Institute for Biology of Ageing, Max Planck Society;

Mourier,  Arnaud
Max Planck Institute for Biology of Ageing, Max Planck Society;

Milenkovic,  Dusanka
Max Planck Institute for Biology of Ageing, Max Planck Society;

Larsson,  Nils-Göran
Max Planck Institute for Biology of Ageing, Max Planck Society;

Filipovska,  Aleksandra
Max Planck Institute for Biology of Ageing, Max Planck Society;

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Zitation

Rackham, O., Busch, J. D., Matic, S., Siira, S. J., Kuznetsova, I., Atanassov, I., et al. (2016). Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly. Cell reports, 16(7), 1874-1890. doi:10.1016/j.celrep.2016.07.031.


Zusammenfassung
The regulation of mitochondrial RNA processing and its importance for ribosome biogenesis and energy metabolism are not clear. We generated conditional knockout mice of the endoribonuclease component of the RNase P complex, MRPP3, and report that it is essential for life and that heart and skeletal-muscle-specific knockout leads to severe cardiomyopathy, indicating that its activity is non-redundant. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-seq enabled us to identify that in vivo 5' tRNA cleavage precedes 3' tRNA processing, and this is required for the correct biogenesis of the mitochondrial ribosomal subunits. We identify that mitoribosomal biogenesis proceeds co-transcriptionally because large mitoribosomal proteins can form a subcomplex on an unprocessed RNA containing the 16S rRNA. Taken together, our data show that RNA processing links transcription to translation via assembly of the mitoribosome.