Pathogenesis-related mutations in the T-loops of human mitochondrial tRNAs affect 3′ end processing and tRNA structure
Pathogenesis-related mutations in the T-loops of human mitochondrial tRNAs affect 3′ end processing and tRNA structure
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DOI：
10.4161/rna.19025
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发表时间：
2012-03-01
期刊：
影响因子：
4.1
通讯作者：
Serjanov, Dmitri
中科院分区：
文献类型：
--
作者：
Levinger, Louis;Serjanov, Dmitri
线粒体基因组中的许多突变与影响肌肉和其他高能量需求组织的母系传播疾病和综合征有关。线粒体基因组通过长双向多顺反子初级转录物编码13个多肽、2个rrna和22个穿插的trna，需要精确切除这些trna。尽管tRNA基因只占线粒体基因组的10%左右，但却包含了大多数与发病相关的突变。tRNase Z核内溶性去除trna前3'预告片。tRNase Z的柔性臂识别并结合前trna的肘部（包括t环）。因此，线粒体tRNA中与发病机制相关的t环突变可能影响tRNA结构，减少tRNase Z结合和3'加工，从而减慢线粒体蛋白质合成。在这里，我们检查了线粒体trna的t环中发病相关突变对trna前结构和tRNase Z加工的影响。线粒体tRNA（Gly）和tRNA（Ile）中59A > G的替换导致K-M增加，并伴随t环结构的变化，表明底物与酶的结合受损。
Numerous mutations in the mitochondrial genome are associated with maternally transmitted diseases and syndromes that affect muscle and other high energy-demand tissues. The mitochondrial genome encodes 13 polypeptides, 2 rRNAs and 22 interspersed tRNAs via long bidirectional polycistronic primary transcripts, requiring precise excision of the tRNAs. Despite making up only similar to 10% of the mitochondrial genome, tRNA genes harbor most of the pathogenesis-related mutations. tRNase Z endonucleolytically removes the pre-tRNA 3' trailer. The flexible arm of tRNase Z recognizes and binds the elbow (including the T-loop) of pre-tRNA. Pathogenesis-related T-loop mutations in mitochondrial tRNAs could thus affect tRNA structure, reduce tRNase Z binding and 3' processing, and consequently slow mitochondrial protein synthesis. Here we inspect the effects of pathogenesis-related mutations in the T-loops of mitochondrial tRNAs on pre-tRNA structure and tRNase Z processing. Increases in K-M arising from 59A > G substitutions in mitochondrial tRNA(Gly) and tRNA(Ile) accompany changes in T-loop structure, suggesting impaired substrate binding to enzyme.