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Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene
The gene encoding mt-tRNA(Leu(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-tRNA(Leu(UUR))...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702489/ https://www.ncbi.nlm.nih.gov/pubmed/17130166 http://dx.doi.org/10.1093/nar/gkl727 |
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author | Maniura-Weber, Katharina Helm, Mark Engemann, Katrin Eckertz, Sabrina Möllers, Myriam Schauen, Matthias Hayrapetyan, Armine von Kleist-Retzow, Jürgen-Christoph Lightowlers, Robert N. Bindoff, Laurence A. Wiesner, Rudolf J. |
author_facet | Maniura-Weber, Katharina Helm, Mark Engemann, Katrin Eckertz, Sabrina Möllers, Myriam Schauen, Matthias Hayrapetyan, Armine von Kleist-Retzow, Jürgen-Christoph Lightowlers, Robert N. Bindoff, Laurence A. Wiesner, Rudolf J. |
author_sort | Maniura-Weber, Katharina |
collection | PubMed |
description | The gene encoding mt-tRNA(Leu(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-tRNA(Leu(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-tRNA(Leu(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. |
format | Text |
id | pubmed-1702489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-17024892006-12-26 Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene Maniura-Weber, Katharina Helm, Mark Engemann, Katrin Eckertz, Sabrina Möllers, Myriam Schauen, Matthias Hayrapetyan, Armine von Kleist-Retzow, Jürgen-Christoph Lightowlers, Robert N. Bindoff, Laurence A. Wiesner, Rudolf J. Nucleic Acids Res Molecular Biology The gene encoding mt-tRNA(Leu(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-tRNA(Leu(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-tRNA(Leu(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. Oxford University Press 2006-12 2006-11-27 /pmc/articles/PMC1702489/ /pubmed/17130166 http://dx.doi.org/10.1093/nar/gkl727 Text en © 2006 The Author(s). |
spellingShingle | Molecular Biology Maniura-Weber, Katharina Helm, Mark Engemann, Katrin Eckertz, Sabrina Möllers, Myriam Schauen, Matthias Hayrapetyan, Armine von Kleist-Retzow, Jürgen-Christoph Lightowlers, Robert N. Bindoff, Laurence A. Wiesner, Rudolf J. Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene |
title | Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene |
title_full | Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene |
title_fullStr | Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene |
title_full_unstemmed | Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene |
title_short | Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA(Leu(UUR))) gene |
title_sort | molecular dysfunction associated with the human mitochondrial 3302a>g mutation in the mttl1 (mt-trna(leu(uur))) gene |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702489/ https://www.ncbi.nlm.nih.gov/pubmed/17130166 http://dx.doi.org/10.1093/nar/gkl727 |
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