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研究鉴定一种RNA聚合酶II磷酸酶INTAC
作者:小柯机器人 发布时间:2020/11/29 22:02:56

复旦大学上海医学院徐彦辉和陈飞课题合作取得最新进展。他们最新研究提出RNA聚合酶II磷酸酶之整合子- PP2A复合物(INTAC)的鉴定。这一研究成果于2020年11月27日发表在国际顶尖学术期刊《科学》杂志上。

他们确定了一个包含整合子和蛋白质磷酸酶2A核心酶(PP2A-AC)的复合物,称为INTAC。3.5埃分辨率的结构揭示了九个人类整合子亚基和PP2A-AC组装成由骨架和肩部模块形成的十字形中央支架,磷酸酶和核酸内切酶模块位于相对侧。作为非经典的PP2A全酶,INTAC复合物可将RNA聚合酶II的羧基末端重复结构域在丝氨酸2,-5和-7位点去磷酸化,从而调节转录。

他们的研究将PP2A的功能扩展到转录调控,并揭示了双重酶活性-RNA裂解和RNA聚合酶II的去磷酸化-在结构和功能上如何整合到INTAC复合物中。

据了解,14亚基后生动物特异性整合子包含一个内切酶,可切割新生的RNA转录物。

附:英文原文

Title: Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase

Author: Hai Zheng, Yilun Qi, Shibin Hu, Xuan Cao, Congling Xu, Zhinang Yin, Xizi Chen, Yan Li, Weida Liu, Jie Li, Jiawei Wang, Gang Wei, Kaiwei Liang, Fei Xavier Chen, Yanhui Xu

Issue&Volume: 2020/11/27

Abstract: The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities—RNA cleavage and RNA polymerase II dephosphorylation—are structurally and functionally integrated into the INTAC complex.

DOI: 10.1126/science.abb5872

Source: https://science.sciencemag.org/content/370/6520/eabb5872

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037