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应激颗粒RNA结合蛋白TIAR-1保护秀丽隐杆线虫的雌性生殖细胞免受热休克影响。

The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock in Caenorhabditis elegans.

作者信息

Huelgas-Morales Gabriela, Silva-García Carlos Giovanni, Salinas Laura S, Greenstein David, Navarro Rosa E

机构信息

Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.

Department of Genetics, Cell Biology and Development, University of Minnesota Minneapolis, 55455 Minnesota

出版信息

G3 (Bethesda). 2016 Apr 7;6(4):1031-47. doi: 10.1534/g3.115.026815.

Abstract

In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germline-the immortal cell lineage required for sexual reproduction-protection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the Caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation; protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures.

摘要

作为对压力条件的响应,真核细胞启动一系列调控程序来保护蛋白质组。一种主要的保护反应涉及蛋白质翻译的停滞以及应激颗粒的形成,应激颗粒是包含保守的RNA结合蛋白TIA-1和TIAR的细胞质核糖核蛋白复合物。应激颗粒反应被认为是在条件改善时保留mRNA用于翻译。对于生殖系细胞——有性生殖所需的永生细胞谱系——免受压力的保护对于物种的延续至关重要,然而应激颗粒调控机制在动物繁殖中的部署方式尚未完全了解。在这里,我们表明应激颗粒蛋白TIAR-1保护秀丽隐杆线虫的生殖系免受热休克的不利影响。与野生型相比,tiar-1中含有强烈功能丧失突变的动物在热休克后生育力显著降低。对热休克蛋白启动子的分析表明tiar-1突变体表现出受损的热休克反应。我们观察到在几种应激条件下,TIAR-1与性腺核心和卵母细胞中的颗粒相关。性腺核心和卵母细胞颗粒都是依赖于翻译的动态结构;蛋白质合成抑制剂改变了它们的形成。尽管如此,tiar-1仅对性腺核心颗粒的形成是必需的。有趣的是,热休克后生殖细胞发育出有活力的胚胎似乎不需要性腺核心颗粒。这表明TIAR-1能够独立于这些结构保护生殖系免受热应激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/4825639/d74ef8c62669/1031f1.jpg

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