TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry

作者全名："Feng, Zhi; Liu, Shengnan; Su, Ming; Song, Chunyu; Lin, Chenyu; Zhao, Fangying; Li, Yang; Zeng, Xianyan; Zhu, Yong; Hou, Yu; Ren, Chunguang; Zhang, Huan; Yi, Ping; Ji, Yong; Wang, Chao; Li, Hongtao; Ma, Ming; Luo, Lingfei; Li, Li"

作者地址："[Feng, Zhi; Su, Ming; Li, Yang; Li, Li] Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Res Ctr Stem Cells & Ageing, Chongqing 400714, Peoples R China; [Liu, Shengnan; Song, Chunyu; Lin, Chenyu; Zhao, Fangying; Li, Hongtao; Ma, Ming; Luo, Lingfei] Southwest Univ, Inst Dev Biol & Regenerat Med, Key Lab Freshwater Fish Reprod & Dev, Minist Educ, Chongqing 400715, Peoples R China; [Zeng, Xianyan; Zhu, Yong; Hou, Yu; Ren, Chunguang; Zhang, Huan] Chongqing Med Univ, Inst Life Sci, Dept Cell Biol & Genet, Lab Dev Biol, Chongqing 400016, Peoples R China; [Yi, Ping] Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China; [Ji, Yong] Nanjing Med Univ, Key Lab Cardiovasc & Cerebrovasc Med, Nanjing 211166, Peoples R China; [Ji, Yong] Nanjing Med Univ, Key Lab Targeted Intervent Cardiovasc Dis, Nanjing 211166, Peoples R China; [Ji, Yong] Nanjing Med Univ, Collaborat Innovat Ctr Cardiovasc Dis Translat Med, Nanjing 211166, Peoples R China; [Ji, Yong] Harbin Med Univ, Natl Key Lab Frigid Zone Cardiovasc Dis NKLFZCD, Harbin 150076, Heilongjiang, Peoples R China; [Wang, Chao] Univ Sci & Technol China, Sch Life Sci, MOE Key Lab Membraneless Organelles & Cellular Dyn, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Peoples R China"

通信作者："Li, L (通讯作者)，Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Res Ctr Stem Cells & Ageing, Chongqing 400714, Peoples R China.; Luo, LF (通讯作者)，Southwest Univ, Inst Dev Biol & Regenerat Med, Key Lab Freshwater Fish Reprod & Dev, Minist Educ, Chongqing 400715, Peoples R China."

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:001185911200028

JCR分区：Q1

影响因子：14.7

年份：2024

卷号：15

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Coat protein complex I (COPI) vesicles mediate the retrograde transfer of cargo between Golgi cisternae and from the Golgi to the endoplasmic reticulum (ER). However, their roles in the cell cycle and proliferation are unclear. This study shows that TANGO6 associates with COPI vesicles via two transmembrane domains. The TANGO6 N- and C-terminal cytoplasmic fragments capture RNA polymerase II subunit B (RPB) 2 in the cis-Golgi during the G1 phase. COPI-docked TANGO6 carries RPB2 to the ER and then to the nucleus. Functional disruption of TANGO6 hinders the nuclear entry of RPB2, which accumulates in the cytoplasm, causing cell cycle arrest in the G1 phase. The conditional depletion or overexpression of TANGO6 in mouse hematopoietic stem cells results in compromised or expanded hematopoiesis. Our study results demonstrate that COPI vesicle-associated TANGO6 plays a role in the regulation of cell cycle progression by directing the nuclear transfer of RPB2, making it a potential target for promoting or arresting cell expansion. How RNA polymerase II subunits enter the nucleus is not well understood. Here, the authors show that Transport and Golgi organization protein 6, TANGO6, recruits RNA polymerase II subunit B2, RPB2, to the ER membrane in a retrograde manner and transports it to the nucleus with the aid of importins."

基金机构："National Natural Science Foundation of China (National Science Foundation of China) [2019YFA802703, 2023YFA1800100]; National Key Research and Development Project [32270873, 31822033]; National Natural Science Foundation of China [CSTB2023TIAD-KPX0056]; Chongqing Population and Health Special Funding of China"

基金资助正文："We thank W. Pan, H. Chen and Y. Guo for mass spectrometry analysis and discussions, B. Zhou, J. Zhou, H. Huang and D. Wang for FACSs technical assistances. This work was supported by National Key Research and Development Project (2019YFA802703, 2023YFA1800100), National Natural Science Foundation of China Grants (32270873, 31822033) and Chongqing Population and Health Special Funding of China (CSTB2023TIAD-KPX0056). The figure models were created with BioRender.com."