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Chinese Journal of Biochemistry and Molecular Biology ; (12): 259-269, 2021.
Artigo em Chinês | WPRIM | ID: wpr-1015963

RESUMO

The discovery of integrator complex (INT) expanded our understanding of noncoding U-rich small nuclear RNA (U snRNA) maturation and transcriptional regulation, and has revived the research boom in related fields. This complex consists of at least 14 subunits, weighting over 1. 4 MD. On one hand, it functions by the cleavage of transcripts; on the other hand, it interacts with protein phosphatase 2A (PP2A) and dephosphorylates the C-terminal repeat sequence of RNA polymerase II (Pol II), thus regulating the transcriptional activity of RNA Pol II, and functions in the production of various RNAs (messenger RNA, small nuclear RNA, enhancer RNA, etc.). INT is recruited to the CTD during transcriptional initiation stage and moves along the U small nuclear RNA (snRNA) gene during transcription. Upon the recognition of 3' maturation sequence element, its cleavage activity is triggered and the matured transcripts are released. Besides, it is also involved in many other processes, including protein-coding gene transcription pause-release, transcriptional elongation, regulation of enhancer RNA transcription, and DNA and RNA metabolism etc. Meanwhile, the significance of INT complex or its components in tumorigenesis, pathogenesis, and ontogeny has being gradually highlighted. Nevertheless, the structural and compositional studies just took a new breakthrough recently. The 14 subunits that make up the complex are characterized by a large number of α-helices, which are further assembled into a huge transcription regulation machine based on the formation of functional modules. This article will mainly discuss about the composition, structural characteristics, functional studies, disease-association, and problem outlook of the integrator complex.

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