Phase separation of BuGZ regulates gut regeneration and aging through interaction with m6A regulators

Qiaoqiao Zhang, Kai Deng, Mengyou Liu, Shengye Yang, Wei Xu, Tong Feng, Minwen Jie, Zhiming Liu, Xiao Sheng, Haiyang Chen () and Hao Jiang ()
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Qiaoqiao Zhang: Sichuan University
Kai Deng: Sichuan University
Mengyou Liu: Sichuan University
Shengye Yang: Sichuan University
Wei Xu: Sichuan University
Tong Feng: Sun Yat-sen University
Minwen Jie: Sichuan University
Zhiming Liu: Sichuan University
Xiao Sheng: Sichuan University
Haiyang Chen: Sichuan University
Hao Jiang: Sichuan University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Exploring the role of phase separation in intracellular compartment formation is an active area of research. However, the associations of phase separation with intestinal stem cell (ISC)-dependent regeneration and aging remain unclear. Here, we demonstrate that BuGZ, a coacervating mitotic effector, shows age- and injury-associated condensation in Drosophila ISC nuclei during interphase. BuGZ condensation promotes ISC proliferation, affecting Drosophila gut repair and longevity. Moreover, m6A reader YT521-B acts as the transcriptional and functional downstream of BuGZ. The binding of YT521-B promotor or m6A writer Ime4/ Mettl14 to BuGZ controls its coacervation, indicating that the promotor may accelerate the phase transition of its binding transcription factor. Hence, we propose that phase separation and m6A regulators may be critical for ameliorating ISC-dependent gut regeneration and aging and requires further study.

Date: 2023
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DOI: 10.1038/s41467-023-42474-1

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