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Cell Rep. 2016 Aug 16;16(7):1874-90. doi: 10.1016/j.celrep.2016.07.031. Epub 2016 Aug 4.

Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly.

Author information

1
Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia; School of Chemistry and Biochemistry, The University of Western Australia, Nedlands, WA 6009, Australia.
2
Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
3
Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
4
Proteomics Core Facility, Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany.
5
Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; CNRS, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, 33077 Bordeaux, France.
6
Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden.
7
Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia; School of Chemistry and Biochemistry, The University of Western Australia, Nedlands, WA 6009, Australia. Electronic address: aleksandra.filipovska@uwa.edu.au.

Abstract

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.

KEYWORDS:

PPR domains; RNA metabolism; RNA-seq; mitochondria

PMID:
27498866
DOI:
10.1016/j.celrep.2016.07.031
[Indexed for MEDLINE]
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