In vitro 3'-end endonucleolytic processing defect in a human mitochondrial tRNA(Ser(UCN)) precursor with the U7445C substitution, which causes non-syndromic deafness.
In vitro 3'-end endonucleolytic processing defect in a human mitochondrial tRNA(Ser(UCN)) precursor with the U7445C substitution, which causes non-syndromic deafness.
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DOI：
10.1093/nar/29.21.4334
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发表时间：
2001-11
影响因子：
14.9
通讯作者：
L. Levinger;Obasanjo Jacobs;Melissa James
中科院分区：
文献类型：
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作者：
L. Levinger;Obasanjo Jacobs;Melissa James
真核生物 tRNA 被转录为前体。在添加 3' 端 CCA、氨酰化、核输出和翻译之前，5' 端前导序列和 3' 端尾随物被 RNase P 和 3'-tRNase 核酸内切去除。 3'-End -CC 可以是 3'-tRNase 抗决定簇，能够防止成熟 tRNA 通过 3'-tRNase 回收。在长的双向线粒体转录本中，22 个 tRNA 点缀着两个 rRNA 和 13 个 mRNA。因此，线粒体基因的准确表达取决于 tRNA 的核酸内切切除。 tRNA 末端加工缺陷可能导致多种线粒体疾病和综合征。人线粒体 L 链转录本中的 U7445C 取代（U74C 直接位于 tRNA(Ser(UCN)) 的鉴别碱基之后）会导致非综合征性耳聋。前体 (G/UCU) 的序列变成 G/CCU，类似于 3'-tRNase 抗决定簇。我们证明具有 U7445C 取代的 tRNA(Ser(UCN)) 前体不能在体外被来自人线粒体的 3'-tRNase 加工。因此，该 tRNA 前体的 3' 端加工缺陷可能是线粒体疾病的原因。
Eukaryotic tRNAs are transcribed as precursors. A 5'-end leader and 3'-end trailer are endonucleolytically removed by RNase P and 3'-tRNase before 3'-end CCA addition, aminoacylation, nuclear export and translation. 3'-End -CC can be a 3'-tRNase anti-determinant with the ability to prevent mature tRNA from recycling through 3'-tRNase. Twenty-two tRNAs punctuate the two rRNAs and 13 mRNAs in long, bidirectional mitochondrial transcripts. Accurate mitochondrial gene expression thus depends on endonucleolytic excision of tRNAs. Various mitochondrial diseases and syndromes could arise from defective tRNA end processing. The U7445C substitution in the human mitochondrial L-strand transcript (U74C directly following the discriminator base of tRNA(Ser(UCN))) causes non-syndromic deafness. The sequence of the precursor (G/UCU) becomes G/CCU, resembling a 3'-tRNase anti-determinant. We demonstrate that a tRNA(Ser(UCN)) precursor with the U7445C substitution cannot be processed in vitro by 3'-tRNase from human mitochondria. A 3'-end processing defect in this tRNA precursor could thus be responsible for mitochondrial disease.