Zhang Rudian, Li Shunjin, Feng Wenzhi, Qian Suhong, Chellappa Akshay John, Wang Fei
UT Southwestern Medical Center, Department of Cell Biology, Dallas, TX, USA.
Currently at Howard Hughes Medical Institute, Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nat Commun. 2025 Jul 1;16(1):5566. doi: 10.1038/s41467-025-60645-0.
Meiosis is more vulnerable to heat than mitosis in many species including humans. In Saccharomyces cerevisiae, we discovered that stress granule formation halts meiosis at high temperatures. Meiotic stress granules appear at lower temperatures (33-42 °C) than mitotic stress granules (~46 °C), requiring the meiosis-specific RNA binding protein Rim4. Heat triggers site-specific Rim4 dephosphorylation, causing it to self-assemble into stress granule seeds. These recruit other stress granule components like Pab1 and mRNAs, pausing meiosis. Normally, 14-3-3 proteins block this assembly by binding phosphorylated Rim4. After temperature drops, Hsp104 assists to break down stress granules. Longer stress granule persistence correlates with better recovery, suggesting stress granules might provide temporal insulation for cellular repair processes prior to meiotic resumption.
在包括人类在内的许多物种中,减数分裂比有丝分裂更容易受到高温的影响。在酿酒酵母中,我们发现应激颗粒的形成会在高温下使减数分裂停止。减数分裂应激颗粒比有丝分裂应激颗粒在更低的温度(33-42°C)下出现,这需要减数分裂特异性RNA结合蛋白Rim4。热触发Rim4位点特异性去磷酸化,使其自组装成应激颗粒种子。这些种子招募其他应激颗粒成分,如Pab1和mRNA,从而使减数分裂暂停。正常情况下,14-3-3蛋白通过结合磷酸化的Rim4来阻止这种组装。温度下降后,Hsp104协助分解应激颗粒。应激颗粒持续时间越长,恢复效果越好,这表明应激颗粒可能在减数分裂恢复之前为细胞修复过程提供时间上的隔离。