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Lookup NU author(s): Professor Robert Lightowlers
The gene encoding mt-tRNALeu(UUR), MT-TL1, is a hotspot for pathogenic mtDNA mutations. Amongst the first to be described was the 3302A>G transition which resulted in a substantial accumulation in patient muscle of RNA19, an unprocessed RNA intermediate including mt-16S rRNA, mt-tRNALeu(UUR) and MTND1. We have now been able to further assess the molecular aetiology associated with 3302A>G in transmitochondrial cybrids. Increased steady-state levels of RNA19 was confirmed, although not to the levels previously reported in muscle. This data was consistent with an increase in RNA19 stability. The mutation resulted in decreased mt-tRNALeu(UUR) levels, but its stability was unchanged, consistent with a defect in RNA19 processing responsible for low tRNA levels. A partial defect in aminoacylation was also identified, potentially caused by an alteration in tRNA structure. These deficiencies lead to a severe defect in respiration in the transmitochondrial cybrids, consistent with the profound mitochondrial disorder originally associated with this mutation. © 2006 Oxford University Press.
Author(s): Maniura-Weber K, Helm M, Engemann K, Eckertz S, Mollers M, Schauen M, Hayrapetyan A, von Kleist-Retzow J-C, Lightowlers RN, Bindoff LA, Wiesner RJ
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Year: 2006
Volume: 34
Issue: 22
Pages: 6404-6415
Print publication date: 01/12/2006
ISSN (print): 0305-1048
ISSN (electronic): 1362-4962
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/nar/gkl727
DOI: 10.1093/nar/gkl727
PubMed id: 17130166
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