应激颗粒的形成与生物学意义

Stress Granule Formation and Its Biological Functions

真核细胞对外界压力刺激会做出一系列应答反应,如暂停蛋白质翻译系统,从而使细胞能更好地适应环境压力。通过应激颗粒(stress granules,SG)的形成包裹未被翻译的mRNA是该适应性调节的重要方式。研究表明,环境压力导致eIF2α上游激酶的激活从而磷酸化eIF2α,翻译起始受阻,随后,TIA-1、TTP等蛋白迅速与mRNP结合聚集成SG,并在微管蛋白的帮助下进一步向细胞核聚集,形成成熟的SG。当压力消失,SG依赖微管及其动力蛋白进行解聚,释放包裹的mRNA及蛋白。细胞内成熟的SG在转录后调节中发挥重要作用,并且通过其组成蛋白在肿瘤凋亡、病毒侵染、免疫、炎症反应及由蛋白错误折叠引起的疾病中发挥作用。该文首次综述了压力颗粒研究进展,为充分认识SG的病理生理性调节功能提供参考。

In response to various types of stress, eukaryote cell activates multiple mechanisms to adapt the environmental changes for survival. The temporal installation of protein translation is one of these mechanisms. Stress granules （SG） which pack lots of untranslated mRNAs rapidly appear as a critical regulator involved in cellular adaptive response. Lines of evidence suggest that SG formation typically begins from phosphorylation of elF2α by the upstream kinases, the phosphorylated elF2α then causes the inhibition of normal translation initiation; subse- quently, many RNA binding proteins such as TIA-1 and TTP combine with these untranslated mRNAs quickly, assembling into complexes which move along microtubule to the nuclear. Once stress disappears, SG dissembles with the help of microtubule and motors, resulting in the release of packed mRNA and proteins. The formed cellular SG is critically involved in the gene post-transcriptional regulation, and plays important roles under a variety of pathological settings such as tumor apoptosis, viral infection, immunity and inflammation. This paper reviews for the first time the current understanding of SG, and will provide useful information for identifying the concrete pathopysiological function of SG.