近日，美国圣犹达儿童研究医院Aseem Z. Ansari及其小组的最新研究提出了细胞信号激酶对RNA聚合酶II的直接靶向和调控。相关论文发表在2025年11月6日出版的《科学》杂志上。

该研究团队查询了约80%的人类激酶，鉴定出117个具有高度位置选择性的磷酸化CTD的激酶。连接这些不同激酶的统一特征是它们选择性地调节信号应答基因上的Pol II。这种“直接基因”调控Pol II的一个例子是表皮生长因子受体（EGFR），一种细胞表面受体酪氨酸激酶。更广泛地说，他们的CTD激酶图谱表明，Pol II是信号转导激酶的直接调控终点，这些激酶控制着细胞生理学，并有助于许多疾病的病因学。

研究人员表示，在基因转录的不同阶段，RNA聚合酶II （Pol II）的羧基末端结构域（CTD）上有不同的磷酸化标记。这些磷酸化CTD标记作为一种分子识别代码，用于募集特定阶段的效应蛋白。

附：英文原文

Title: Direct targeting and regulation of RNA polymerase II by cell signaling kinases

Author: Preeti Dabas, Meritxell B. Cutrona, Wojciech Rosikiewicz, Ryan P. Kempen, Patrick Rodrigues, John Bowling, Mollie S. Prater, Walter H. Lang, Adithi Danda, Zhi Yuan, Beisi Xu, Shondra M. Pruett-Miller, Gang Wu, Taosheng Chen, Aseem Z. Ansari

Issue&Volume: 2025-11-06

Abstract: Distinct phosphorylation marks are placed on the carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) during different stages of gene transcription. These phospho-CTD marks function as a molecular recognition code for the recruitment of stage-specific effector proteins. Querying ~80% of the human kinome, we identified 117 kinases that phosphorylate the CTD with a high degree of positional selectivity. The unifying characteristic linking these diverse kinases is that they selectively regulate Pol II at signal-responsive genes. An example of such “direct-at-gene” Pol II regulation is displayed by epidermal growth factor receptor (EGFR), a cell surface receptor tyrosine kinase. More broadly, our atlas of CTD kinases implicates Pol II as a direct regulatory end point for signal-transducing kinases that govern cellular physiology and contribute to the etiology of numerous diseases.

DOI: ads7152

Source: https://www.science.org/doi/10.1126/science.ads7152