The 7472insC mitochondrial DNA mutation impairs the synthesis and extent of aminoacylation of tRNASer(UCN) but not its structure or rate of turnover

The Journal of Biological Chemistry
Marina ToompuuH T Jacobs

Abstract

The 7472insC mitochondrial DNA mutation in the tRNA(Ser(UCN)) gene is associated with sensorineural deafness combined, in some patients, with a wider neurological syndrome. In cultured cybrid cells it causes a 70% decrease in tRNA(Ser(UCN)) abundance and mild respiratory impairment, previously suggested to be due to decreased tRNA stability. When mitochondrial transcription was blocked by ethidium bromide treatment, the half-life of the mutant tRNA was not significantly different from that of wild-type tRNA(Ser(UCN)). Over-expression of mitochondrial translational elongation factor EF-Tu also had no effect on the mutant phenotype. However, during recovery from prolonged ethidium bromide treatment, the synthesis of the mutant tRNA(Ser(UCN)) was specifically impaired, without polarity effects on downstream tRNAs of the light strand transcription unit. We infer that the mutation acts posttranscriptionally to decrease tRNA(Ser(UCN)) abundance by affecting its synthesis rather than its stability. The extent of aminoacylation of the mutant tRNA was also decreased by approximately 25%. In contrast, the mutation had no detectable effect on tRNA(Ser(UCN)) base modification or structure other than the insertion of an extra guanosine temp...Continue Reading

References

Nov 25, 1991·Nucleic Acids Research·T YokogawaK Watanabe
Jul 14, 1989·Cell·G CarraraG P Tocchini-Valentini
Jan 25, 1988·Nucleic Acids Research·J L KruppN C Martin
Jan 1, 1987·Methods in Enzymology·Y KuchinoS Nishimura
Nov 28, 1969·Journal of Molecular Biology·E Zylber, S Penman
Apr 9, 1981·Nature·S AndersonI G Young
Sep 5, 1995·Biochemical and Biophysical Research Communications·M NakamuraJ Kimura
May 26, 1995·The Journal of Biological Chemistry·W RossmanithE Sbisà
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·J A Enríquez, G Attardi
Aug 1, 1996·Annals of Neurology·P KaufmannE A Schon
Feb 21, 1998·Nucleic Acids Research·M SprinzlS Steinberg
Apr 16, 1998·Nature Genetics·A El MezianeH T Jacobs
Mar 27, 1999·European Journal of Human Genetics : EJHG·K VerhoevenG Van Camp
Apr 7, 1999·Journal of Molecular Biology·M NashimotoR L Kaspar
Mar 4, 2000·Human Molecular Genetics·G V BörnerS Pääbo
May 10, 2000·The Journal of Biological Chemistry·Y C CaiL L Spremulli
May 29, 2000·The Journal of Biological Chemistry·J N SpelbrinkH T Jacobs
Jul 8, 2000·Brain Pathology·S DiMauro, A L Andreu
Oct 4, 2000·Nature Structural Biology·S O KelleyP Schimmel

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Citations

Nov 11, 2003·Trends in Biochemical Sciences·Lisa M Wittenhagen, Shana O Kelley
Jan 3, 2007·Cell Research·Guangqian XingXin Cao
Aug 21, 2003·Human Molecular Genetics·Howard T Jacobs
Oct 13, 2004·Nucleic Acids Research·Louis LevingerCatherine Florentz
May 17, 2013·Nucleic Acids Research·Tanit GuitartLluís Ribas de Pouplana
Sep 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jiqiang LingMichael Ibba
Apr 28, 2012·Mitochondrion·Jing ZhengMin-Xin Guan
Feb 24, 2015·Journal of the American Chemical Society·Anthony M MustoeCharles L Brooks
Sep 16, 2005·The EMBO Journal·Sarin ChimnaronkKimitsuna Watanabe
Nov 14, 2007·Muscle & Nerve·Fernando Scaglia, Lee-Jun C Wong
Feb 8, 2005·Biochemical and Biophysical Research Communications·Xiaoming LiMin-Xin Guan
Sep 1, 2004·Biochemical and Biophysical Research Communications·Marina ToompuuHoward T Jacobs
Oct 16, 2004·Neuromuscular Disorders : NMD·Vincenza FetoniMassimo Zeviani
Apr 15, 2004·Biochemical and Biophysical Research Communications·William J GibbonsMin-Xin Guan
May 17, 2014·Nucleic Acids Research·Takeo Suzuki, Tsutomu Suzuki
Aug 5, 2004·European Journal of Human Genetics : EJHG·Howard T JacobsRobert F Mueller
Jan 18, 2020·RNA Biology·Christopher A Powell, Michal Minczuk
Jul 31, 2019·Nucleic Acids Research·Jean-Michel CarterShobbir Hussain
Aug 30, 2020·Nature Communications·Takeo SuzukiTsutomu Suzuki
Mar 9, 2018·Nucleic Acids Research·Marina ToompuuHoward T Jacobs
Nov 11, 2020·Biochimica Et Biophysica Acta. Bioenergetics·Michele Brischigliaro, Massimo Zeviani

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