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Structure of the catalytic core of the Integrator complex.

ABSTRACT: The Integrator is a specialized 3' end-processing complex involved in cleavage and transcription termination of a subset of nascent RNA polymerase II transcripts, including small nuclear RNAs (snRNAs). We provide evidence of the modular nature of the Integrator complex by biochemically characterizing its two subcomplexes, INTS5/8 and INTS10/13/14. Using cryoelectron microscopy (cryo-EM), we determined a 3.5-Å-resolution structure of the INTS4/9/11 ternary complex, which constitutes Integrator's catalytic core. Our structure reveals the spatial organization of the catalytic nuclease INTS11, bound to its catalytically impaired homolog INTS9 via several interdependent interfaces. INTS4, a helical repeat protein, plays a key role in stabilizing nuclease domains and other components. In this assembly, all three proteins form a composite electropositive groove, suggesting a putative RNA binding path within the complex. Comparison with other 3' end-processing machineries points to distinct features and a unique architecture of the Integrator's catalytic module.

SUBMITTER: Pfleiderer MM

PROVIDER: S-EPMC7980224 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Structure of the catalytic core of the Integrator complex.

Pfleiderer Moritz M MM Galej Wojciech P WP

Molecular cell 20210205 6

The Integrator is a specialized 3' end-processing complex involved in cleavage and transcription termination of a subset of nascent RNA polymerase II transcripts, including small nuclear RNAs (snRNAs). We provide evidence of the modular nature of the Integrator complex by biochemically characterizing its two subcomplexes, INTS5/8 and INTS10/13/14. Using cryoelectron microscopy (cryo-EM), we determined a 3.5-Å-resolution structure of the INTS4/9/11 ternary complex, which constitutes Integrator's ...[more]

PMID: 33548203

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