7SN8

Cryo-EM structure of Drosophila Integrator cleavage module (IntS4-IntS9-IntS11) in complex with IP6

Summary for 7SN8

• Entry DOI: 10.2210/pdb7sn8/pdb
• EMDB information: 25214
• Descriptor: Integrator complex subunit 4, Integrator complex subunit 11, Integrator complex subunit 9, ... (5 entities in total)
• Functional Keywords: integrator, inositol hexakisphosphate, nuclease
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 3
• Total formula weight: 256555.18

Authors

Lin, M.,Tong, L. (deposition date: 2021-10-27, release date: 2022-10-12, Last modification date: 2025-06-04)

Primary citation

Lin, M.H.,Jensen, M.K.,Elrod, N.D.,Huang, K.L.,Welle, K.A.,Wagner, E.J.,Tong, L.
Inositol hexakisphosphate is required for Integrator function.
Nat Commun, 13:5742-5742, 2022

PubMed Abstract: Integrator 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 Å resolution, revealing stable association of an inositol hexakisphosphate (IP) molecule. The IP binding site is located in a highly electropositive pocket at an interface among all three subunits of ICM, 55 Å away from the IntS11 active site and generally conserved in other ICMs. We also confirmed IP association with the same site in human ICM. IP binding is not detected in ICM samples harboring mutations in this binding site. Such mutations or disruption of IP biosynthesis significantly reduced Integrator function in snRNA 3'-end processing and mRNA transcription attenuation. Our structural and functional studies reveal that IP is required for Integrator function in Drosophila, humans, and likely other organisms.

PubMed: 36180473
DOI: 10.1038/s41467-022-33506-3

Experimental method

ELECTRON MICROSCOPY (2.74 Å)