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CTDK-I 在细胞中的多种作用。

Multiple roles of CTDK-I throughout the cell.

机构信息

Plant Molecular Biology and Genetic Engineering Division, CSIR-National Botanical Research Institute, Lucknow, U.P., 226001, India.

Department of Molecular and Life Science, College of Science and Convergence Technology, Hanyang University ERICA Campus, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea.

出版信息

Cell Mol Life Sci. 2019 Jul;76(14):2789-2797. doi: 10.1007/s00018-019-03118-0. Epub 2019 Apr 29.

Abstract

The heterotrimeric carboxy-terminal domain kinase I (CTDK-I) in yeast is a cyclin-dependent kinase complex that is evolutionally conserved throughout eukaryotes and phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (RNApII) on the second-position serine (Ser2) residue of YSPTSPS heptapeptide repeats. CTDK-I plays indispensable roles in transcription elongation and transcription-coupled processing, such as the 3'-end processing of nascent mRNA transcripts. However, recent studies have revealed additional roles of CTDK-I beyond its primary effect on transcription by RNApII. Here, we describe recent advances in the regulation of genomic stability and rDNA integrity by CTDK-I and highlight the previously underappreciated cellular roles of CTDK-I in rRNA synthesis by RNA polymerase I and translational initiation and elongation. These multiple roles of CTDK-I throughout the cell expand our understanding of how this complex functions to coordinate diverse cellular processes through gene expression and how the human orthologue exerts its roles in diseased states such as tumorigenesis.

摘要

酵母中的异三聚体羧基末端结构域激酶 I (CTDK-I) 是一种细胞周期蛋白依赖性激酶复合物,在真核生物中高度保守,可磷酸化 RNA 聚合酶 II (RNApII) 大亚基的 C 末端结构域上的第二位置丝氨酸(Ser2)残基上的 YSPTSPS 七肽重复序列。CTDK-I 在转录延伸和转录偶联加工中发挥不可或缺的作用,例如新生 mRNA 转录本的 3'-末端加工。然而,最近的研究揭示了 CTDK-I 除了对 RNApII 转录的主要影响之外的其他作用。在这里,我们描述了 CTDK-I 对基因组稳定性和 rDNA 完整性的调控的最新进展,并强调了 CTDK-I 在 RNA 聚合酶 I 介导的 rRNA 合成以及翻译起始和延伸中以前未被充分认识的细胞作用。CTDK-I 在整个细胞中的这些多种作用扩展了我们对该复合物如何通过基因表达协调多种细胞过程的理解,以及人类同源物如何在肿瘤发生等疾病状态下发挥其作用。

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