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-Structure paper
タイトル | Assembly mechanism of Integrator's RNA cleavage module. |
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ジャーナル・号・ページ | Mol Cell, Vol. 84, Issue 15, Page 2882-2899.e10, Year 2024 |
掲載日 | 2024年8月8日 |
著者 | Kevin Sabath / Chunhong Qiu / Stefanie Jonas / |
PubMed 要旨 | The modular Integrator complex is a transcription regulator that is essential for embryonic development. It attenuates coding gene expression via premature transcription termination and performs 3'- ...The modular Integrator complex is a transcription regulator that is essential for embryonic development. It attenuates coding gene expression via premature transcription termination and performs 3'-processing of non-coding RNAs. For both activities, Integrator requires endonuclease activity that is harbored by an RNA cleavage module consisting of INTS4-9-11. How correct assembly of Integrator modules is achieved remains unknown. Here, we show that BRAT1 and WDR73 are critical biogenesis factors for the human cleavage module. They maintain INTS9-11 inactive during maturation by physically blocking the endonuclease active site and prevent premature INTS4 association. Furthermore, BRAT1 facilitates import of INTS9-11 into the nucleus, where it is joined by INTS4. Final BRAT1 release requires locking of the mature cleavage module conformation by inositol hexaphosphate (IP). Our data explain several neurodevelopmental disorders caused by BRAT1, WDR73, and INTS11 mutations as Integrator assembly defects and reveal that IP is an essential co-factor for cleavage module maturation. |
リンク | Mol Cell / PubMed:39032489 |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.9 Å |
構造データ | EMDB-18833, PDB-8r22: EMDB-18834, PDB-8r23: EMDB-18839, PDB-8r2d: |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | TRANSCRIPTION / Chaperone / nuclear import / Integrator complex |