Human mitochondrial diseases caused by lack of taurine modification in mitochondrial tRNAs.

Abstract

Mitochondrial DNA mutations that cause mitochondrial dysfunction are responsible for a wide spectrum of human diseases, referred to as mitochondrial diseases. Pathogenic point mutations are found frequently in genes encoding mitochondrial (mt) tRNAs, indicating that impaired functioning of mutant mt tRNAs is the primary cause of mitochondrial dysfunction. Our previous studies revealed the absence of posttranscriptional taurine modification at the anticodon wobble uridine in mutant mt tRNAs isolated from cells derived from patients with two major classes of mitochondrial diseases, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonus epilepsy associated with ragged red fibers). Defective taurine modification of the mutant mt tRNAs results in a deficiency in protein synthesis as the cognate codons of the mutant mt tRNA cannot be decoded. These findings represent the first evidence of a molecular pathogenesis caused by an RNA modification disorder.

• Authors: Tsutomu Suzuki, Asuteka Nagao, Takeo Suzuki
• Journal: Wiley interdisciplinary reviews. RNA (Wiley Interdiscip Rev RNA) 2011 May-Jun Vol. 2 Issue 3 Pg. 376-86 ISSN: 1757-7012 [Electronic] United States
• PMID: 21957023 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• RNA, Mitochondrial
• Taurine
• RNA
• RNA, Transfer

Topics

• Base Sequence
• Humans
• MELAS Syndrome (etiology, genetics, metabolism)
• MERRF Syndrome (etiology, genetics, metabolism)
• Mitochondrial Diseases (etiology, genetics, metabolism)
• Models, Biological
• Models, Molecular
• Molecular Sequence Data
• Nucleic Acid Conformation
• Point Mutation
• RNA (chemistry, genetics, metabolism)
• RNA Processing, Post-Transcriptional
• RNA Stability
• RNA, Mitochondrial
• RNA, Transfer (chemistry, genetics, metabolism)
• Taurine (chemistry, metabolism)