CTDP1 and RPB7 stabilize Pol II and permit reinitiation
Abstract The mechanisms governing the termination and subsequent reinitiation of RNA polymerase II (Pol II) remain poorly understood. Here we find that depletion of RPB7 leads to the destabilization of Pol II’s largest subunit, RPB1. This destabilization is influenced by the loop regions of RPB7, CD...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57513-2 |
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| author | Haonan Zheng Qiqin Xu Dexun Ji Boqin Yang Xiong Ji |
| author_facet | Haonan Zheng Qiqin Xu Dexun Ji Boqin Yang Xiong Ji |
| author_sort | Haonan Zheng |
| collection | DOAJ |
| description | Abstract The mechanisms governing the termination and subsequent reinitiation of RNA polymerase II (Pol II) remain poorly understood. Here we find that depletion of RPB7 leads to the destabilization of Pol II’s largest subunit, RPB1. This destabilization is influenced by the loop regions of RPB7, CDK9, the C-terminal domain (CTD) of RPB1, and its linker region. The stabilization process of RPB1 is regulated by the E3 ubiquitin ligase Cullin 3. Additionally, RPB7 interacts with the phosphatase CTDP1, which is crucial for maintaining RPB1 stability. RPB7 is also vital for the reinitiation of Pol II, engages with RNA processing factors, and is localized to the RNA exit channel of the Pol II complex. The absence of RPB7 compromises RNA processing. We propose that RPB7 recruits CTDP1 to dephosphorylate Pol II, enhancing its stability and facilitating efficient reinitiation, adding an emerging dimension to transcriptional regulation. |
| format | Article |
| id | doaj-art-74295f1ed33f4f3ab668cb00fa62636e |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-74295f1ed33f4f3ab668cb00fa62636e2025-08-20T03:05:45ZengNature PortfolioNature Communications2041-17232025-03-0116111810.1038/s41467-025-57513-2CTDP1 and RPB7 stabilize Pol II and permit reinitiationHaonan Zheng0Qiqin Xu1Dexun Ji2Boqin Yang3Xiong Ji4State Key Laboratory of Gene Function and Modulation Research, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, Beijing Advanced Center of RNA Biology (BEACON), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking UniversityState Key Laboratory of Gene Function and Modulation Research, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, Beijing Advanced Center of RNA Biology (BEACON), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking UniversityState Key Laboratory of Gene Function and Modulation Research, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, Beijing Advanced Center of RNA Biology (BEACON), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking UniversityState Key Laboratory of Gene Function and Modulation Research, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, Beijing Advanced Center of RNA Biology (BEACON), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking UniversityState Key Laboratory of Gene Function and Modulation Research, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, Beijing Advanced Center of RNA Biology (BEACON), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking UniversityAbstract The mechanisms governing the termination and subsequent reinitiation of RNA polymerase II (Pol II) remain poorly understood. Here we find that depletion of RPB7 leads to the destabilization of Pol II’s largest subunit, RPB1. This destabilization is influenced by the loop regions of RPB7, CDK9, the C-terminal domain (CTD) of RPB1, and its linker region. The stabilization process of RPB1 is regulated by the E3 ubiquitin ligase Cullin 3. Additionally, RPB7 interacts with the phosphatase CTDP1, which is crucial for maintaining RPB1 stability. RPB7 is also vital for the reinitiation of Pol II, engages with RNA processing factors, and is localized to the RNA exit channel of the Pol II complex. The absence of RPB7 compromises RNA processing. We propose that RPB7 recruits CTDP1 to dephosphorylate Pol II, enhancing its stability and facilitating efficient reinitiation, adding an emerging dimension to transcriptional regulation.https://doi.org/10.1038/s41467-025-57513-2 |
| spellingShingle | Haonan Zheng Qiqin Xu Dexun Ji Boqin Yang Xiong Ji CTDP1 and RPB7 stabilize Pol II and permit reinitiation Nature Communications |
| title | CTDP1 and RPB7 stabilize Pol II and permit reinitiation |
| title_full | CTDP1 and RPB7 stabilize Pol II and permit reinitiation |
| title_fullStr | CTDP1 and RPB7 stabilize Pol II and permit reinitiation |
| title_full_unstemmed | CTDP1 and RPB7 stabilize Pol II and permit reinitiation |
| title_short | CTDP1 and RPB7 stabilize Pol II and permit reinitiation |
| title_sort | ctdp1 and rpb7 stabilize pol ii and permit reinitiation |
| url | https://doi.org/10.1038/s41467-025-57513-2 |
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