Identification of STAU1 as a regulator of HBV replication by TurboID-based proximity labeling

Wei, Xia-Fei1,2; Fan, Shu-Ying1; Wang, Yu-Wei3; Li, Shan1; Long, Shao-Yuan1; Gan, Chun-Yang1; Li, Jie1; Sun, Yu-Xue1; Guo, Lin1; Wang, Pei-Yun1; Yang, Xue1; Wang, Jin-Lan1; Cui, Jing1; Zhang, Wen-Lu1; Huang, Ai-Long1; Hu, Jie-Li1

2022-06-17

10.1016/j.isci.2022.104416

ISCIENCE   Impact Factor & Quartile

2589-0042

The core promoter (CP) of hepatitis B virus (HBV) is critical for HBV replication by controlling the transcription of pregenomic RNA (pgRNA). Host factors regulating the activity of the CP can be identified by different methods. Biotin-based proximity labeling, a powerful method with the capability to capture weak or dynamic interactions, has not yet been used to map proteins interacting with the CP. Here, we established a strategy, based on the newly evolved promiscuous enzyme TurboID, for interrogating host factors regulating the activity of HBV CP. Using this strategy, we identified STAU1 as an important factor involved in the regulation of HBV CP. Mechanistically, STAU1 indirectly binds to CP mediated by TARDBP, and recruits the SAGA transcription coactivator complex to the CP to upregulate its activity. Moreover, STAU1 binds to HBx and enhances the level of HBx by stabilizing it in a ubiquitin-independent manner.

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National Natural Science Foundation of China[81871635,81671997,"U20A20392",81902060] ; Natural Science Foundation of Chongqing["cstc2021jcyjmsxmX0298","cstc2020jcyj-msxmX0764","cstc2020jscx-dxwtBX0022"] ; 111 Project[D20028] ; Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University[202104] ; CQMU Program for Youth Innovation in Future Medicine[W0049] ; Talent Development Program of CQMU for Postgraduate[BJRC201903]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000809491300001

CELL PRESS

Web of Science

1.Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Inst Hepatol, Shenzhen, Peoples R China
3.Chongqing Hosp Tradit Chinese Med, Dept Lab Med, Chongqing, Peoples R China

Wei, Xia-Fei,Fan, Shu-Ying,Wang, Yu-Wei,et al. Identification of STAU1 as a regulator of HBV replication by TurboID-based proximity labeling[J]. ISCIENCE,2022,25(6).

Wei, Xia-Fei.,Fan, Shu-Ying.,Wang, Yu-Wei.,Li, Shan.,Long, Shao-Yuan.,...&Hu, Jie-Li.(2022).Identification of STAU1 as a regulator of HBV replication by TurboID-based proximity labeling.ISCIENCE,25(6).

Wei, Xia-Fei,et al."Identification of STAU1 as a regulator of HBV replication by TurboID-based proximity labeling".ISCIENCE 25.6(2022).