Laboratory for Aging and Cancer Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
Laboratory of Metabolism and Aging Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
Nat Commun. 2023 Oct 23;14(1):6700. doi: 10.1038/s41467-023-42474-1.
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, mA reader YT521-B acts as the transcriptional and functional downstream of BuGZ. The binding of YT521-B promotor or mA 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 mA regulators may be critical for ameliorating ISC-dependent gut regeneration and aging and requires further study.
探索相分离在细胞内隔室形成中的作用是一个活跃的研究领域。然而，相分离与肠干细胞（ISC）依赖性再生和衰老的关联尚不清楚。在这里，我们证明了 BuGZ，一种凝聚有丝分裂效应物，在果蝇 ISC 核的间期表现出与年龄和损伤相关的凝聚。BuGZ 凝聚促进 ISC 增殖，影响果蝇肠道修复和寿命。此外，mA 阅读器 YT521-B 作为 BuGZ 的转录和功能下游发挥作用。YT521-B 启动子或 mA 书写器 Ime4/Mettl14 与 BuGZ 的结合控制其凝聚，表明启动子可能加速其结合转录因子的相变。因此，我们提出相分离和 mA 调节剂可能对改善 ISC 依赖性肠道再生和衰老至关重要，需要进一步研究。
