Pathogenesis-related mutations in the T-loops of human mitochondrial tRNAs affect 3' end processing and tRNA structure.

RNA Biology
Louis Levinger, Dmitri Serjanov

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.

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Citations

Jan 16, 2016·Life·Jinwei Zhang, Adrian R Ferré-D'Amaré
May 29, 2015·Journal of Inherited Metabolic Disease·Lindsey Van HauteMichal Minczuk
Jul 16, 2013·American Journal of Human Genetics·Tobias B HaackHolger Prokisch
Sep 27, 2020·Acta neurologica Belgica·Marwa MaalejFaiza Fakhfakh
May 24, 2021·The Journal of Biological Chemistry·Yanchun JiMin-Xin Guan

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