title: Defects in RNA metabolism in mitochondrial disease.
abstract: The expression of mitochondrially-encoded genes requires the efficient processing of long precursor RNAs at the 5' and 3' ends of tRNAs, a process which, when disrupted, results in disease. Two such mutations reside within mt-tRNALeu(UUR); a m.3243A>G transition, which is the most common cause of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), and m.3302A>G which often causes mitochondrial myopathy (MM). We used parallel analysis of RNA ends (PARE) that captures the 5' terminal end of 5'-monophosphorylated mitochondrial RNAs to compare the effects of the m.3243A>G and m.3302A>G mutations on mitochondrial tRNA processing and downstream RNA metabolism. We confirmed previously identified RNA processing defects, identified common internal cleavage sites and new sites unique to the m.3243A>G mutants that do not correspond to transcript ends. These sites occur in regions of predicted RNA secondary structure, or are in close proximity to such regions, and may identify regions of importance to the processing of mtRNAs.
authors.affiliation: Harry Perkins Institute of Medical Research and Centre for Medical Research, Level 7 QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA 6009, Australia.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Siira
authors.affiliation: Harry Perkins Institute of Medical Research and Centre for Medical Research, Level 7 QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA 6009, Australia.
authors.forename: Anne-Marie J
authors.initials: AJ
authors.lastname: Shearwood
authors.affiliation: Division of Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Bracken
authors.affiliation: Harry Perkins Institute of Medical Research and Centre for Medical Research, Level 7 QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Molecular Sciences, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Rackham
authors.affiliation: Harry Perkins Institute of Medical Research and Centre for Medical Research, Level 7 QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Molecular Sciences, The University of Western Australia, Nedlands, Western Australia 6009, Australia. Electronic address: aleksandra.filipovska@uwa.edu.au.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Filipovska
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics*; D009154:Mutation; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D000077278:RNA, Mitochondrial; D017423:Sequence Analysis, RNA
chemical_list: D000077278:RNA, Mitochondrial; D012313:RNA
keywords: Mitochondrial disease; PARE; RNA metabolism; tRNA