title: Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly.
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.
authors: 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.
authors: Oliver
authors: O
authors: Rackham
authors: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Jakob D
authors: JD
authors: Busch
authors: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Stanka
authors: S
authors: Matic
authors: Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
authors: Stefan J
authors: SJ
authors: Siira
authors: Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
authors: Irina
authors: I
authors: Kuznetsova
authors: Proteomics Core Facility, Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany.
authors: Ilian
authors: I
authors: Atanassov
authors: Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
authors: Judith A
authors: JA
authors: Ermer
authors: Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
authors: Anne-Marie J
authors: AM
authors: Shearwood
authors: Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
authors: Tara R
authors: TR
authors: Richman
authors: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: James B
authors: JB
authors: Stewart
authors: 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.
authors: Arnaud
authors: A
authors: Mourier
authors: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Dusanka
authors: D
authors: Milenkovic
authors: 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.
authors: Nils-Göran
authors: NG
authors: Larsson
authors: 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.
authors: Aleksandra
authors: A
authors: Filipovska
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002458:Cell Fractionation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D000069396:Mitochondrial Ribosomes / Q000378:metabolism*; D018482:Muscle, Skeletal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D001678:Organelle Biogenesis; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D043262:Ribonuclease P / Q000172:deficiency / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D024101:Mitochondrial Proteins; D012336:RNA, Ribosomal, 16S; D012269:Ribosomal Proteins; D012343:RNA, Transfer; D043262:Ribonuclease P
keywords: PPR domains; RNA metabolism; RNA-seq; mitochondria