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

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.