Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-University Freiburg, Freiburg, 79104, Germany.
Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University Freiburg, Freiburg, 79104, Germany.
Nat Commun. 2023 Jul 13;14(1):4176. doi: 10.1038/s41467-023-39882-8.
Transient stress experiences not only trigger acute stress responses, but can also have long-lasting effects on cellular functions. In Caenorhabditis elegans, a brief exposure to heat shock during early adulthood extends lifespan and improves stress resistance, a phenomenon known as heat hormesis. Here, we investigated the prolonged effect of hormetic heat stress on the transcriptome of worms and found that the canonical heat shock response is followed by a profound transcriptional reprogramming in the post-stress period. This reprogramming relies on the endoribonuclease ENDU-2 but not the heat shock factor 1. ENDU-2 co-localizes with chromatin and interacts with RNA polymerase II, enabling specific regulation of transcription after the stress period. Failure to activate the post-stress response does not affect the resistance of animals to heat shock but eliminates the beneficial effects of hormetic heat stress. In summary, our work discovers that the RNA-binding protein ENDU-2 mediates the long-term impacts of transient heat stress via reprogramming transcriptome after stress exposure.
瞬时应激经历不仅会引发急性应激反应，还会对细胞功能产生持久影响。在秀丽隐杆线虫中，成年早期短暂暴露于热休克会延长寿命并提高应激抗性，这种现象称为热应激。在这里，我们研究了热应激对蠕虫转录组的长期影响，发现经典的热休克反应之后是应激后时期的深刻转录重编程。这种重编程依赖于内切核糖核酸酶 ENDU-2，但不依赖于热休克因子 1。ENDU-2 与染色质共定位，并与 RNA 聚合酶 II 相互作用，使应激后能够特异性调节转录。未能激活应激后反应不会影响动物对热休克的抗性，但会消除热应激的有益影响。总之，我们的工作发现，RNA 结合蛋白 ENDU-2 通过在应激暴露后重编程转录组来介导短暂热应激的长期影响。
