Journal
CELL REPORTS
Volume 16, Issue 7, Pages 1874-1890Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.07.031
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Funding
- National Health and Medical Research Council [APP1058442, APP1045677, APP1041582, APP1023460, APP1005030, APP1043978]
- Australian Research Council
- Cancer Council of Western Australia
- Swedish Research Council [Radsprofessor 2015-0418]
- Knut and Alice Wallenbergs Foundation
- Alexander von Humboldt Foundation
- EMBO Short-Term Scholarship
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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 50 tRNA cleavage precedes 30 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.
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