The 7SK snRNP complex: a critical regulator in carcinogenesis.

Biochimie Pub Date : 2025-05-12 DOI:10.1016/j.biochi.2025.05.003

Oriana Puidebat, Sylvain Egloff

{"title":"The 7SK snRNP complex: a critical regulator in carcinogenesis.","authors":"Oriana Puidebat, Sylvain Egloff","doi":"10.1016/j.biochi.2025.05.003","DOIUrl":null,"url":null,"abstract":"<p><p>Cyclin-Dependent Kinase 9 (CDK9) is a critical regulator of transcriptional elongation, functioning within the Positive Transcription Elongation Factor b (P-TEFb) complex alongside Cyclin T1. P-TEFb facilitates the release of RNA polymerase II (RNAPII) from promoter-proximal pausing, thereby enabling productive transcriptional elongation. CDK9 activity is tightly controlled by the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex, comprising 7SK snRNA, LARP7, MEPCE, and HEXIM1/2. Under homeostatic conditions, the 7SK snRNP sequesters and inactivates a fraction of P-TEFb, maintaining it in a repressed state. However, in response to cellular stress or increased transcriptional demand, P-TEFb is released from 7SK snRNP, activating CDK9 to ensure precise, context-dependent transcriptional control. This regulatory switch allows dynamic adaptation to environmental and intracellular cues. Emerging evidence implicates 7SK snRNP deregulation in cancer progression. This review explores the intricate interplay between 7SK snRNP and CDK9, highlighting how disruptions in individual 7SK snRNP components drive transcriptional imbalances, amplify oncogenic programs, and promote a tumorigenic environment.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimie","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.biochi.2025.05.003","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Cyclin-Dependent Kinase 9 (CDK9) is a critical regulator of transcriptional elongation, functioning within the Positive Transcription Elongation Factor b (P-TEFb) complex alongside Cyclin T1. P-TEFb facilitates the release of RNA polymerase II (RNAPII) from promoter-proximal pausing, thereby enabling productive transcriptional elongation. CDK9 activity is tightly controlled by the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex, comprising 7SK snRNA, LARP7, MEPCE, and HEXIM1/2. Under homeostatic conditions, the 7SK snRNP sequesters and inactivates a fraction of P-TEFb, maintaining it in a repressed state. However, in response to cellular stress or increased transcriptional demand, P-TEFb is released from 7SK snRNP, activating CDK9 to ensure precise, context-dependent transcriptional control. This regulatory switch allows dynamic adaptation to environmental and intracellular cues. Emerging evidence implicates 7SK snRNP deregulation in cancer progression. This review explores the intricate interplay between 7SK snRNP and CDK9, highlighting how disruptions in individual 7SK snRNP components drive transcriptional imbalances, amplify oncogenic programs, and promote a tumorigenic environment.

查看原文本刊更多论文

7SK snRNP复合体：癌变的关键调控因子。

细胞周期蛋白依赖性激酶9 （CDK9）是转录延伸的关键调节因子，与细胞周期蛋白T1一起在正转录延伸因子b （P-TEFb）复合体中发挥作用。P-TEFb促进启动子近端暂停释放RNA聚合酶II (RNAPII)，从而实现高效转录延伸。CDK9的活性受到7SK小核核糖核蛋白（7SK snRNP）复合物的严格控制，该复合物包括7SK snRNA、LARP7、MEPCE和HEXIM1/2。在稳态条件下，7SK snRNP隔离和失活P-TEFb的一部分，使其保持在抑制状态。然而，在细胞应激或转录需求增加的情况下，P-TEFb从7SK snRNP中释放，激活CDK9以确保精确的、依赖于上下文的转录控制。这种调节开关允许对环境和细胞内信号进行动态适应。新出现的证据暗示7SK snRNP在癌症进展中失调。这篇综述探讨了7SK snRNP和CDK9之间复杂的相互作用，强调了单个7SK snRNP组分的破坏如何驱动转录失衡，放大致癌程序，并促进致瘤环境。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biochimie

自引率

0.00%

发文量