Format

Send to

Choose Destination
See comment in PubMed Commons below
RNA Biol. 2005 Apr;2(2):41-4. Epub 2005 Apr 14.

Human mitochondrial diseases associated with tRNA wobble modification deficiency.

Author information

  • 1Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8565, Japan.

Abstract

A growing number of mutations in mitochondrial (mt) tRNA genes have been found to associate with human mitochondrial diseases. Our previous analysis of mutant mt tRNAs isolated from cells derived from patients with mitochondrial diseases revealed the lack of a post-transcriptional taurine-modification at the anticodon wobble uridine in two mt tRNAs bearing typical pathogenic mutations: mt tRNA(Leu(UUR)) with either the MELAS 3243 or 3271 mutation and mt tRNA(Lys) with the MERRF 8344 mutation. We here summarize our recent studies that clarify the molecular basis of the defective mitochondrial translation caused by this wobble modification deficiency. The MERRF mt tRNA(Lys) lacking the wobble modification cannot translate either of its codons (AAA and AAG), while the translational activity of MELAS mt tRNA(Leu(UUR)) lacking wobble modification is more depressed in decoding of UUG codon than UUA codon. These findings suggest that the wobble modification deficiency plays a primary role in the molecular pathogenesis of the MELAS and MERRF mitochondrial diseases.

PMID:
17132941
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Support Center