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Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNALeu(UUR)) gene

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.

Publication metadata

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


DOI: 10.1093/nar/gkl727

PubMed id: 17130166


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Funder referenceFunder name
074454Wellcome Trust