2. Academic Validation
  3. TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry

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

  • Nat Commun. 2024 Mar 15;15(1):2371. doi: 10.1038/s41467-024-46720-y.
Zhi Feng # 1,  Shengnan Liu # 2,  Ming Su 1,  Chunyu Song 2,  Chenyu Lin 2,  Fangying Zhao 2,  Yang Li 1,  Xianyan Zeng 3,  Yong Zhu 3,  Yu Hou 3,  Chunguang Ren 3,  Huan Zhang 3,  Ping Yi 4,  Yong Ji 5 6,  Chao Wang 7,  Hongtao Li 2,  Ming Ma 2,  Lingfei Luo 8,  Li Li 9
Affiliations

Affiliations

  • 1 Research center of Stem cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, PR China.
  • 2 Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing, 400715, PR China.
  • 3 Institute of Life Sciences, Laboratory of Developmental Biology, Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, 400016, PR China.
  • 4 Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China.
  • 5 Key Laboratory of Cardiovascular and Cerebrovascular Medicine; Key Laboratory of Targeted Intervention of Cardiovascular Disease; Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, PR China.
  • 6 National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin, 150076, Heilongjiang, PR China.
  • 7 MOE Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, PR China.
  • 8 Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing, 400715, PR China. lluo@swu.edu.cn.
  • 9 Research center of Stem cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, PR China. lili@cigit.ac.cn.
  • # Contributed equally.
PMID: 38490996 DOI: 10.1038/s41467-024-46720-y
Abstract

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.

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