5v8w | pdb_00005v8w
Crystal structure of human Integrator IntS9-IntS11 CTD complex
Structural highlights
Function[INT9_HUMAN] Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. [INT11_HUMAN] Catalytic component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates the snRNAs 3' cleavage.[1] Publication Abstract from PubMedThe metazoan Integrator complex (INT) has important functions in the 3'-end processing of noncoding RNAs, including the uridine-rich small nuclear RNA (UsnRNA) and enhancer RNA (eRNA), and in the transcription of coding genes by RNA polymerase II. The INT contains at least 14 subunits, but its molecular mechanism of action is poorly understood, because currently there is little structural information about its subunits. The endonuclease activity of INT is mediated by its subunit 11 (IntS11), which belongs to the metallo-beta-lactamase superfamily and is a paralog of CPSF-73, the endonuclease for pre-mRNA 3'-end processing. IntS11 forms a stable complex with Integrator complex subunit 9 (IntS9) through their C-terminal domains (CTDs). Here, we report the crystal structure of the IntS9-IntS11 CTD complex at 2.1-A resolution and detailed, structure-based biochemical and functional studies. The complex is composed of a continuous nine-stranded beta-sheet with four strands from IntS9 and five from IntS11. Highly conserved residues are located in the extensive interface between the two CTDs. Yeast two-hybrid assays and coimmunoprecipitation experiments confirm the structural observations on the complex. Functional studies demonstrate that the IntS9-IntS11 interaction is crucial for the role of INT in snRNA 3'-end processing. Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance.,Wu Y, Albrecht TR, Baillat D, Wagner EJ, Tong L Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):4394-4399. doi:, 10.1073/pnas.1616605114. Epub 2017 Apr 10. PMID:28396433[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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