title: RNA processing in human mitochondria.
abstract: Mammalian mitochondrial DNA is transcribed as precursor polycistronic transcripts containing 13 mRNAs, 2 rRNAs, punctuated by 22 tRNAs. The mechanisms involved in the excision of mitochondrial tRNAs from these polycistronic transcripts have remained largely unknown. We have investigated the roles of ELAC2, mitochondrial RNase P proteins 1 and 3, and pentatricopeptide repeat domain protein 1 in the processing of mitochondrial polycistronic transcripts. We used a deep sequencing approach to characterize the 5' and 3' ends of processed mitochondrial transcripts and provide a detailed map of mitochondrial tRNA processing sites affected by these proteins. We show that MRPP1 and MRPP3 process the 5' ends of tRNAs and the 5' unconventional, non tRNA containing site of the CO1 transcript. By contrast, we find that ELAC2 and PTCD1 affect the 3' end processing of tRNAs. Finally, we found that MRPP1 is essential for transcript processing, RNA modification, translation and mitochondrial respiration.
authors.affiliation: Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, WA Australia.
authors.forename: Maria I G Lopez
authors.initials: MI
authors.lastname: Sanchez
authors.forename: Tim R
authors.initials: TR
authors.lastname: Mercer
authors.forename: Stefan M K
authors.initials: SM
authors.lastname: Davies
authors.forename: Anne-Marie J
authors.initials: AM
authors.lastname: Shearwood
authors.forename: Karoline K A
authors.initials: KK
authors.lastname: Nygård
authors.forename: Tara R
authors.initials: TR
authors.lastname: Richman
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
authors.forename: Oliver
authors.initials: O
authors.lastname: Rackham
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Filipovska
mesh_terms: D015152:Blotting, Northern; D019069:Cell Respiration; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D050259:Genes, Mitochondrial; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043262:Ribonuclease P / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014162:Transfection
chemical_list: C421605:ELAC2 protein, human; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; C544933:PTCD1 protein, human; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012313:RNA; D012343:RNA, Transfer; D043262:Ribonuclease P