title: Pathogenesis-related mutations in the T-loops of human mitochondrial tRNAs affect 3' end processing and tRNA structure.
abstract: Numerous mutations in the mitochondrial genome are associated with maternally transmitted diseases and syndromes that affect muscle and other high energy-demand tissues. The mitochondrial genome encodes 13 polypeptides, 2 rRNAs and 22 interspersed tRNAs via long bidirectional polycistronic primary transcripts, requiring precise excision of the tRNAs. Despite making up only ~10% of the mitochondrial genome, tRNA genes harbor most of the pathogenesis-related mutations. tRNase Z endonucleolytically removes the pre-tRNA 3' trailer. The flexible arm of tRNase Z recognizes and binds the elbow (including the T-loop) of pre-tRNA. Pathogenesis-related T-loop mutations in mitochondrial tRNAs could thus affect tRNA structure, reduce tRNase Z binding and 3' processing, and consequently slow mitochondrial protein synthesis. Here we inspect the effects of pathogenesis-related mutations in the T-loops of mitochondrial tRNAs on pre-tRNA structure and tRNase Z processing. Increases in K(M) arising from 59A > G substitutions in mitochondrial tRNA(Gly) and tRNA(Ile) accompany changes in T-loop structure, suggesting impaired substrate binding to enzyme.
authors.affiliation: York College of The City University of New York, Jamaica, NY, USA. llevinger@york.cuny.edu
authors.forename: Louis
authors.initials: L
authors.lastname: Levinger
authors.forename: Dmitri
authors.initials: D
authors.lastname: Serjanov
mesh_terms: D001483:Base Sequence; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D026721:RNA 3' End Processing; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012322:RNA Precursors; D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer; D004722:Endoribonucleases