Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
PLoS Pathog. 2024 Oct 31;20(10):e1012666. doi: 10.1371/journal.ppat.1012666. eCollection 2024 Oct.
Stress granules (SGs) are stress-induced RNA condensates consisting of stalled initiation complexes resulting from translational inhibition. The biochemical composition and function of SGs are highly diverse, and this diversity has been attributed to different stress conditions, signalling pathways involved and specific cell types. Interestingly, mRNA decay components, which are found in ubiquitous cytoplasmic foci known as processing bodies (PB), have also been identified in SG proteomes. A major challenge in current SG studies is to understand the cause of SG diversity, as well as the function of SG under different stress conditions. Trypanosoma brucei is a single-cellular parasite that causes Human African Trypanosomiasis (sleeping sickness). In this study, we showed that by varying the supply of extracellular carbon sources during starvation, cellular ATP levels changed rapidly, resulting in SGs of different compositions and dynamics. We identified a subset of SG components, which dissociated from the SGs in response to cellular ATP depletion. Using expansion microscopy, we observed sub-granular compartmentalization of PB- and SG-components within the stress granules. Our results highlight the importance of cellular ATP in SG composition and dynamics, providing functional insight to SGs formed under different stress conditions.
应激颗粒（SGs）是应激诱导的 RNA 凝聚物，由翻译抑制引起的停滞起始复合物组成。SGs 的生化组成和功能高度多样化，这种多样性归因于不同的应激条件、涉及的信号通路和特定的细胞类型。有趣的是，在普遍存在的细胞质焦点中发现的 mRNA 衰变成分，也被鉴定为处理体（PB）中的 SG 蛋白质组。目前 SG 研究的主要挑战是了解 SG 多样性的原因，以及在不同应激条件下 SG 的功能。布氏锥虫是一种单细胞寄生虫，会引起人类非洲锥虫病（昏睡病）。在这项研究中，我们表明，通过在饥饿期间改变细胞外碳源的供应，细胞内的 ATP 水平迅速变化，导致 SG 具有不同的组成和动力学。我们鉴定了一组 SG 成分，这些成分在细胞内 ATP 耗尽时从 SG 中解离出来。使用扩展显微镜，我们观察到 PB 和 SG 成分在应激颗粒内的亚颗粒区室化。我们的结果强调了细胞内 ATP 在 SG 组成和动力学中的重要性，为不同应激条件下形成的 SG 提供了功能见解。
