Maturation of selected human mitochondrial tRNAs requires deadenylation
Maturation of selected human mitochondrial tRNAs requires deadenylation
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DOI：
10.7554/elife.27596
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发表时间：
2017-07-26
期刊：
影响因子：
7.7
通讯作者：
Minczuk, Michal
中科院分区：
文献类型：
--
作者：
Pearce, Sarah F.;Rorbach, Joanna;Minczuk, Michal
人类线粒体含有编码氧化磷酸化系统的必需亚基的基因组（mtDNA）。mtDNA的表达需要前体RNA的多步成熟。在其他系统中，RNA生命周期涉及监视机制，然而，RNA质量控制的细节尚未在人类线粒体中得到广泛表征。使用线粒体核糖体分析和线粒体多聚（A）-尾RNA测序（MPAT-Seq）测定，我们鉴定了多聚（A）-特异性核糖核酸外切酶PDE 12作为线粒体非编码RNA质量控制的主要因素。PDE 12的缺乏导致线粒体（mt-）rRNA和mt-tRNA的3'端的假聚腺苷酸化。虽然16 S mt-rRNA的异常腺苷酸化并不影响线粒体的完整性，但在mt-tRNA中添加虚假的poly（A）导致某些mt-tRNA的氨酰化池水平降低，并且线粒体在相应的密码子处停滞。因此，我们的数据揭示了人类线粒体中一种新的、依赖于去腺苷酸化的mtDNA成熟途径。
Human mitochondria contain a genome (mtDNA) that encodes essential subunits of the oxidative phosphorylation system. Expression of mtDNA entails multi-step maturation of precursor RNA. In other systems, the RNA life cycle involves surveillance mechanisms, however, the details of RNA quality control have not been extensively characterised in human mitochondria. Using a mitochondrial ribosome profiling and mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) assay, we identify the poly(A)-specific exoribonuclease PDE12 as a major factor for the quality control of mitochondrial non-coding RNAs. The lack of PDE12 results in a spurious polyadenylation of the 3' ends of the mitochondrial (mt-) rRNA and mt-tRNA. While the aberrant adenylation of 16S mt-rRNA did not affect the integrity of the mitoribosome, spurious poly(A) additions to mt-tRNA led to reduced levels of aminoacylated pool of certain mt-tRNAs and mitoribosome stalling at the corresponding codons. Therefore, our data uncover a new, deadenylation-dependent mtRNA maturation pathway in human mitochondria.