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-Structure paper
タイトル | Inositol hexakisphosphate is required for Integrator function. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 5742, Year 2022 |
掲載日 | 2022年9月30日 |
著者 | Min-Han Lin / Madeline K Jensen / Nathan D Elrod / Kai-Lieh Huang / Kevin A Welle / Eric J Wagner / Liang Tong / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:36180473 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.74 Å |
構造データ | EMDB-25214, PDB-7sn8: |
化合物 | ChemComp-ZN: ChemComp-IHP: |
由来 |
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キーワード | NUCLEASE (ヌクレアーゼ) / integrator (積分器) / inositol hexakisphosphate (フィチン酸) |