7sn8
Cryo-EM structure of Drosophila Integrator cleavage module (IntS4-IntS9-IntS11) in complex with IP6
Structural highlights
FunctionINT4_DROME Component of the Integrator complex, a complex involved in the transcription of small nuclear RNAs (snRNA) and their 3'-box-dependent processing (PubMed:21078872, PubMed:23097424). Involved in the 3'-end processing of the U7 snRNA, and also the spliceosomal snRNAs U1, U2, U4 and U5 (PubMed:21078872, PubMed:23097424). Essential for development (PubMed:21078872). May mediate recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex (By similarity).[UniProtKB:Q96HW7][1] [2] Publication Abstract from PubMedIntegrator is a multi-subunit protein complex associated with RNA polymerase II (Pol II), with critical roles in noncoding RNA 3'-end processing and transcription attenuation of a broad collection of mRNAs. IntS11 is the endonuclease for RNA cleavage, as a part of the IntS4-IntS9-IntS11 Integrator cleavage module (ICM). Here we report a cryo-EM structure of the Drosophila ICM, at 2.74 A resolution, revealing stable association of an inositol hexakisphosphate (IP(6)) molecule. The IP(6) binding site is located in a highly electropositive pocket at an interface among all three subunits of ICM, 55 A away from the IntS11 active site and generally conserved in other ICMs. We also confirmed IP(6) association with the same site in human ICM. IP(6) binding is not detected in ICM samples harboring mutations in this binding site. Such mutations or disruption of IP(6) biosynthesis significantly reduced Integrator function in snRNA 3'-end processing and mRNA transcription attenuation. Our structural and functional studies reveal that IP(6) is required for Integrator function in Drosophila, humans, and likely other organisms. , PMID:36180473[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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