University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Department of Human Genetics, Biomedical Research Building, Room 719, 1501 NW 10th Avenue, Miami, FL 33136, USA.
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Department of Human Genetics, Biomedical Research Building, Room 719, 1501 NW 10th Avenue, Miami, FL 33136, USA.
Curr Opin Cell Biol. 2021 Jun;70:37-43. doi: 10.1016/j.ceb.2020.11.003. Epub 2020 Dec 16.
Genomic transcription is fundamental to all organisms. In metazoans, the Integrator complex is required for endonucleolytic processing of noncoding RNAs, regulation of RNA polymerase II pause-release, and premature transcription attenuation at coding genes. Recent insights into the structural composition and evolution of Integrator subunits have informed our understanding of its biochemical functionality. Moreover, studies in multiple model organisms point to an essential function of Integrator in signaling response and cellular development, highlighting a key role in neuronal differentiation. Indeed, alterations in Integrator complex subunits have been identified in patients with neurodevelopmental diseases and cancer. Taken together, we propose that Integrator is a central regulator of transcriptional processes and that its evolution reflects genomic complexity in regulatory elements and chromatin architecture.
基因组转录是所有生物的基础。在后生动物中，整合体复合物对于非编码 RNA 的内切核酸酶加工、RNA 聚合酶 II 暂停释放的调节以及编码基因的转录过早衰减是必需的。最近对整合体亚基的结构组成和进化的深入了解，使我们对其生化功能有了更深入的认识。此外，在多种模式生物中的研究表明，整合体在信号反应和细胞发育中具有重要功能，突出了其在神经元分化中的关键作用。事实上，已经在患有神经发育疾病和癌症的患者中发现了整合体复合物亚基的改变。综上所述，我们提出整合体是转录过程的中央调节剂，其进化反映了调节元件和染色质结构的基因组复杂性。
