Journal
SCIENCE
Volume 370, Issue 6520, Pages 1059-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abb5872
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Funding
- National Key R&D program of China [2016YFA0500700]
- National Natural Science Foundation of China [31830107, 32030055, 31821002, 32070636]
- National Ten-Thousand Talent Program
- National Program for support of Top-Notch Young Professionals
- Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]
- Shanghai Municipal Science and Technology Commission [19JC1411500]
- Shanghai Natural Science Foundation [20ZR1412100]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB08000000]
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The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities-RNA cleavage and RNA polymerase II dephosphorylation-are structurally and functionally integrated into the INTAC complex.
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