Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNALeu(UUR)) gene.
Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNALeu(UUR)) gene.
复制标题
与人线粒体3302a> g突变相关的分子功能障碍（mt-trnaleu（uur））基因中的分子功能障碍。
DOI：
10.1093/nar/gkl727
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发表时间：
2006
影响因子：
14.9
通讯作者：
Wiesner, Rudolf J.
中科院分区：
文献类型：
--
作者：
Maniura-Weber, Katharina;Helm, Mark;Engemann, Katrin;Eckertz, Sabrina;Moellers, Myriam;Schauen, Matthias;Hayrapetyan, Armine;von Kleist-Retzow, Juergen-Christoph;Lightowlers, Robert N.;Bindoff, Laurence A.;Wiesner, Rudolf J.
编码mt-tRNALeu(UUR)的基因MT-TL1是mtDNA致病突变的热点。首先要描述的是3302a>；G转换，它导致RNA19在患者肌肉中大量积累，RNA19是一种未经处理的RNA中间体，包括mt-16S rRNA、mt-tRNALeu(UUR)和MTND1。我们现在已经能够进一步评估与传递线粒体囊体中的3302a和gt；G相关的分子病原学。RNA19的稳定水平增加得到了证实，尽管没有达到之前在肌肉中报道的水平。这一数据与RNA19稳定性的增加是一致的。该突变导致mt-tRNALeu(UUR)水平下降，但其稳定性没有变化，这与导致tRNA水平低的RNA19加工缺陷一致。氨基酰化的部分缺陷也被发现，可能是由于tRNA结构的改变引起的。这些缺陷导致传递线粒体胞体的呼吸严重缺陷，这与最初与该突变相关的严重线粒体疾病一致。
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.
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影响因子：
64.8
作者：
GOTO, Y;NONAKA, I;HORAI, S
通讯作者：
HORAI, S
DOI：
10.1073/pnas.78.9.5623
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BLAU, HM;WEBSTER, C
通讯作者：
WEBSTER, C
影响因子：
30.8
作者：
ENRIQUEZ, JA;CHOMYN, A;ATTARDI, G
通讯作者：
ATTARDI, G
影响因子：
3.5
作者：
Rossmanith, W;Karwan, RM
通讯作者：
Karwan, RM
影响因子：
3.5
作者：
Börner, GV;Zeviani, M;Pääbo, S
通讯作者：
Pääbo, S