{"title":"The Integrator-PP2A complex integrates promoter-proximal premature termination with chromatin context and genome maintenance.","authors":"Aixia Song, Danyi Lu, Fei Xavier Chen","doi":"10.1016/j.tibs.2025.09.006","DOIUrl":null,"url":null,"abstract":"<p><p>Well-regulated transcription is essential for maintaining cellular homeostasis and genome integrity. The Integrator-PP2A complex has emerged as a major regulator of transcription by stimulating promoter-proximal termination of RNA polymerase II (Pol II). By employing dual catalytic activities, Integrator-PP2A shapes transcriptional output, limits aberrant RNA production, and suppresses R-loop-associated genome instability. Integrator-PP2A is highly modular, enabling dynamic interactions with transcription factors and epigenetic modifiers in distinct chromatin contexts and serving as a molecular hub that links transcriptional regulation to RNA quality control, chromatin state, and genome surveillance. Here, we review recent insights into the composition, mechanisms, and regulatory functions of this complex, which together establish its broad roles across both coding and noncoding transcriptional programs.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0000,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Biochemical Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tibs.2025.09.006","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Well-regulated transcription is essential for maintaining cellular homeostasis and genome integrity. The Integrator-PP2A complex has emerged as a major regulator of transcription by stimulating promoter-proximal termination of RNA polymerase II (Pol II). By employing dual catalytic activities, Integrator-PP2A shapes transcriptional output, limits aberrant RNA production, and suppresses R-loop-associated genome instability. Integrator-PP2A is highly modular, enabling dynamic interactions with transcription factors and epigenetic modifiers in distinct chromatin contexts and serving as a molecular hub that links transcriptional regulation to RNA quality control, chromatin state, and genome surveillance. Here, we review recent insights into the composition, mechanisms, and regulatory functions of this complex, which together establish its broad roles across both coding and noncoding transcriptional programs.
期刊介绍：
For over 40 years, Trends in Biochemical Sciences (TIBS) has been a leading publication keeping readers informed about recent advances in all areas of biochemistry and molecular biology. Through monthly, peer-reviewed issues, TIBS covers a wide range of topics, from traditional subjects like protein structure and function to emerging areas in signaling and metabolism. Articles are curated by the Editor and authored by top researchers in their fields, with a focus on moving beyond simple literature summaries to providing novel insights and perspectives. Each issue primarily features concise and timely Reviews and Opinions, supplemented by shorter articles including Spotlights, Forums, and Technology of the Month, as well as impactful pieces like Science & Society and Scientific Life articles.
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