Arnold Jamie J, Smidansky Eric D, Moustafa Ibrahim M, Cameron Craig E
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):948-60. doi: 10.1016/j.bbagrm.2012.04.002. Epub 2012 Apr 19.
Transcription of the human mitochondrial genome is required for the expression of 13 subunits of the respiratory chain complexes involved in oxidative phosphorylation, which is responsible for meeting the cells' energy demands in the form of ATP. Also transcribed are the two rRNAs and 22 tRNAs required for mitochondrial translation. This process is accomplished, with the help of several accessory proteins, by the human mitochondrial RNA polymerase (POLRMT, also known as h-mtRNAP), a nuclear-encoded single-subunit DNA-dependent RNA polymerase (DdRp or RNAP) that is distantly related to the bacteriophage T7 class of single-subunit RNAPs. In addition to its role in transcription, POLRMT serves as the primase for mitochondrial DNA replication. Therefore, this enzyme is of fundamental importance for both expression and replication of the human mitochondrial genome. Over the past several years rapid progress has occurred in understanding POLRMT and elucidating the molecular mechanisms of mitochondrial transcription. Important accomplishments include development of recombinant systems that reconstitute human mitochondrial transcription in vitro, determination of the X-ray crystal structure of POLRMT, identification of distinct mechanisms for promoter recognition and transcription initiation, elucidation of the kinetic mechanism for POLRMT-catalyzed nucleotide incorporation and discovery of unique mechanisms of mitochondrial transcription inhibition including the realization that POLRMT is an off target for antiviral ribonucleoside analogs. This review summarizes the current understanding of POLRMT structure-function, mechanism and inhibition. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.
人类线粒体基因组的转录对于参与氧化磷酸化的呼吸链复合物的13个亚基的表达是必需的，氧化磷酸化负责以ATP的形式满足细胞的能量需求。线粒体翻译所需的两种rRNA和22种tRNA也会被转录。这一过程是在几种辅助蛋白的帮助下，由人类线粒体RNA聚合酶（POLRMT，也称为h-mtRNAP）完成的，它是一种核编码的单亚基DNA依赖性RNA聚合酶（DdRp或RNAP），与噬菌体T7类单亚基RNAPs有较远的亲缘关系。除了在转录中的作用外，POLRMT还作为线粒体DNA复制的引发酶。因此，这种酶对于人类线粒体基因组的表达和复制都至关重要。在过去几年里，在理解POLRMT和阐明线粒体转录的分子机制方面取得了迅速进展。重要成果包括开发了在体外重建人类线粒体转录的重组系统、确定了POLRMT的X射线晶体结构、识别了启动子识别和转录起始的不同机制、阐明了POLRMT催化核苷酸掺入的动力学机制以及发现了线粒体转录抑制的独特机制，包括认识到POLRMT是抗病毒核糖核苷类似物的脱靶对象。本综述总结了目前对POLRMT结构功能、机制和抑制的理解。本文是名为“线粒体基因表达”的特刊的一部分。
