Diverse Functions of mRNA Metabolism Factors in Stress Defense and Aging of <i>Caenorhabditis elegans</i>

Processing bodies (PBs) and stress granules (SGs) are related, cytoplasmic RNA-protein complexes that contribute to post-transcriptional gene regulation in all eukaryotic cells. Both structures contain translationally repressed mRNAs and several proteins involved in silencing, stabilization or degradation of mRNAs, especially under environmental stress. Here, we monitored the dynamic formation of PBs and SGs, in somatic cells of adult worms, using fluorescently tagged protein markers of each complex. Both complexes were accumulated in response to various stress conditions, but distinct modes of SG formation were induced, depending on the insult. We also observed an age-dependent accumulation of PBs but not of SGs. We further showed that direct alterations in PB-related genes can influence aging and normal stress responses, beyond their developmental role. In addition, disruption of SG-related genes had diverse effects on development, fertility, lifespan and stress resistance of worms. Our work therefore underlines the important roles of mRNA metabolism factors in several vital cellular processes and provides insight into their diverse functions in a multicellular organism.处理小体（Processing bodies, PBs）与应激颗粒（Stress granules, SGs）是一类相关的细胞质核糖核蛋白复合物，在所有真核细胞中均参与转录后基因调控。两类结构均包含翻译抑制的信使RNA（mRNA）以及多种参与mRNA沉默、稳定或降解的蛋白质，尤其在环境应激状态下发挥作用。本研究通过分别靶向两类复合物的荧光标记蛋白标志物，监测了成年线虫体细胞中PBs与SGs的动态形成过程。研究发现，两类复合物的积累均响应多种应激条件，但应激颗粒的形成存在不同的诱导模式，具体取决于应激原的类型。此外，我们观察到处理小体的积累呈年龄依赖性，而应激颗粒则无此现象。我们进一步证实，直接改变与处理小体相关的基因，可影响线虫的衰老进程与正常应激应答，这一作用超出了这些基因在发育过程中的功能范畴。另外，干扰应激颗粒相关基因，会对线虫的发育、繁殖力、寿命及应激抗性产生多样影响。综上，本研究凸显了mRNA代谢因子在诸多关键细胞过程中的重要作用，并为解析其在多细胞生物中的多样功能提供了新视角。