The research team comprehensively utilized cell lines and animal models such as mice to reveal a new mechanism by which TANGO6 regulates RPB2 entry into the nucleus through COPI vesicle transport, driving cell proliferation, and emphasized its important role in promoting hematopoietic stem cell expansion. This study was published in the top international journal 《Nature Communications》 with the title "TANGO6 regulations cell promotion via COPIVES mediated RPB2 nuclear entry".
This study reports for the first time that TANGO6 is anchored to COPI vesicles through two transmembrane domains, carrying RPB2 (the second largest subunit of RNA polymerase II). Subsequently, membrane fusion is mediated by the SNARE complex and enters the endoplasmic reticulum. With the assistance of the endoplasmic reticulum resident protein LRRC59, it reaches the nuclear pore complex and interacts with the nuclear input protein KPNB1 to enter the nucleus. Further confirmation confirms that TANGO6 carrying RPB2 is crucial for driving cell proliferation through COPI vesicle transport mediated nuclear transfer, and this mechanism is essential for the amplification of mouse HSCs. The new mechanism of TANGO6 regulating cell proliferation through COPI vesicle transport revealed in this study provides a new reference for effectively amplifying HSCs or serving as a potential target to alleviate and treat tumors.
Feng Zhi, Special Research Assistant of Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, and Liu Shengnan, PhD candidate of Southwest University, are the co first author of the paper. Li Li, a researcher of the Chinese Academy of Sciences Chongqing Institute of Green and Intelligent Technology, and Luo Lingfei, a professor of Southwest University, are the co corresponding authors. At the same time, the study received guidance and assistance from Professor Ma Ming from Southwest University, Professor Zhu Yong and Hou Yu from Chongqing Medical University, as well as Professor Ren Chunguang, Professor Yi Ping from the Third Affiliated Hospital of Chongqing Medical University, and Professor Ji Yong from Nanjing Medical University/Harbin Medical University.
The above work was supported by the National Key R&D Program, the National Natural Science Foundation of China and the Hundred Talents Program of the Chinese Academy of Sciences.
Journal Introduction: The latest impact factor of Nature Communications is 16.6. It is an internationally peer-reviewed multidisciplinary open access journal dedicated to publishing high-quality research in various fields such as biology, medicine, health, physics, chemistry, and earth sciences. Original link: https://www.nature.com/articles/s41467-024-46720-y.pdf