Phase separation controls Drosophila intestinal stem cell proliferation during gut regeneration and aging by modulating of m6A regulators

Exploring the antennas of phase separation forming intracellular compartmentation becomes hot recently. However, the associations of phase separation with intestinal stem cell (ISC)-dependent regeneration and aging are still unknown. Here, we demonstrate that BuGZ, a coacervating protein playing an important role during mitosis, shows age- and injury-associated elevation of protein levels and coacervation behavior in stem cell nuclei during interphase. The phase separation of BuGZ promotes ISC proliferation, which affects the intestinal functions and lifespan of Drosophila upon aging and tissue regeneration. Moreover, this study shows that m6A reader YT521-B acts as the transcriptional and functional downstream of BuGZ. The binding of BuGZ to the YT521-B promotor facilitates its coacervation, indicating that the promotor may accelerate the phase transition of its binding transcription factor. Furthermore, m6A writers (Ime4 and Mett14) interact with BuGZ in the ISCs, inhibiting its phase separation. Hence, we propose that phase separation and m6A regulators may be the hallmarks of studying and fixing ISC-dependent regeneration and aging. Here, this project stored the raw sequencing data associated with this study.