在高等真核生物中，调节RNA聚合酶II（Pol II）的活动，对编码蛋白质基因和许多非编码RNA进行微调的关键在于Pol II的调节活动。整合素复合物是唯一与Pol II相关的大型多蛋白复合物，它是后生动物特有的，因此长期以来一直被研究忽视。整合素由至少14个亚基组成，这些亚基被分成不同的功能模块。核心催化模块的磷酸二酯酶活性在转录过程中针对多种RNA物种，包括长非编码RNA（lncRNA）、U小核RNA（U snRNA）、PIWI相互作用RNA（piRNA）、增强子RNA和新生前mRNA等。整合素对非编码RNA的处理对其生物发生至关重要，在编码蛋白基因上，整合素是Pol II启动子近端停滞和转录延伸的关键调节因子。最近的研究发现了一个整合素特异性的丝氨酸/苏氨酸蛋白磷酸酶2A（PP2A）模块，它针对Pol II和其他基础转录机制的组件。在本综述中，我们讨论了整合素的活动如何调节转录、RNA加工、染色质景观和DNA修复。我们还讨论了整合素在发育和肿瘤发生中的多样化作用。©2022 Springer Nature Limited。

In higher eukaryotes, fine-tuned activation of protein-coding genes and many non-coding RNAs pivots around the regulated activity of RNA polymerase II (Pol II). The Integrator complex is the only Pol II-associated large multiprotein complex that is metazoan specific, and has therefore been understudied for years. Integrator comprises at least 14 subunits, which are grouped into distinct functional modules. The phosphodiesterase activity of the core catalytic module is co-transcriptionally directed against several RNA species, including long non-coding RNAs (lncRNAs), U small nuclear RNAs (U snRNAs), PIWI-interacting RNAs (piRNAs), enhancer RNAs and nascent pre-mRNAs. Processing of non-coding RNAs by Integrator is essential for their biogenesis, and at protein-coding genes, Integrator is a key modulator of Pol II promoter-proximal pausing and transcript elongation. Recent studies have identified an Integrator-specific serine/threonine-protein phosphatase 2A (PP2A) module, which targets Pol II and other components of the basal transcription machinery. In this Review, we discuss how the activity of Integrator regulates transcription, RNA processing, chromatin landscape and DNA repair. We also discuss the diverse roles of Integrator in development and tumorigenesis.© 2022. Springer Nature Limited.