Sabath Kevin, Jonas Stefanie
Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Switzerland.
Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Switzerland.
Curr Opin Struct Biol. 2022 Dec;77:102443. doi: 10.1016/j.sbi.2022.102443. Epub 2022 Sep 8.
The metazoan-specific Integrator complex is a >1.5 MDa machinery that interacts with RNA polymerase II (RNAP2) to attenuate coding gene transcription by early termination close to transcription start sites. Using a highly related mechanism, Integrator also performs the initial 3'-end processing step for many non-coding RNAs. Its transcription regulation functions are essential for cell differentiation and response to external stimuli. Recent studies revealed that the complex incorporates phosphatase PP2A to counteract phosphorylation reactions that are required for transcription elongation. Structures of Integrator bound to RNAP2 explain the basis for its recruitment to promoter proximal RNAP2 by recognition of its paused state. Furthermore, several studies indicate that Integrator's cleavage activity is regulated at multiple levels through activators, modifications, and small molecules.
后生动物特有的整合酶复合体是一种分子量超过1.5 MDa的机制，它与RNA聚合酶II（RNAP2）相互作用，通过在转录起始位点附近提前终止来减弱编码基因的转录。利用高度相关的机制，整合酶还对许多非编码RNA进行初始3'端加工步骤。其转录调控功能对于细胞分化和对外部刺激的反应至关重要。最近的研究表明，该复合体包含磷酸酶PP2A，以抵消转录延伸所需的磷酸化反应。与RNAP2结合的整合酶结构解释了通过识别其暂停状态将其招募到启动子近端RNAP2的基础。此外，多项研究表明，整合酶的切割活性通过激活剂、修饰和小分子在多个水平上受到调控。
