Stress-specific differences in assembly and composition of stress granules and related foci
Stress-specific differences in assembly and composition of stress granules and related foci
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DOI：
10.1242/jcs.199240
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发表时间：
2017-03-01
影响因子：
4
通讯作者：
Ivanov, Pavel
中科院分区：
文献类型：
--
作者：
Aulas, Anais;Fay, Marta M.;Ivanov, Pavel
细胞已经发展出不同的机制来响应压力，包括形成被称为压力颗粒（SG）的细胞质病灶。SGs是动态的，并且由于应激诱导的翻译抑制而形成。尽管由于SG对几种人类疾病的发病机制的贡献而对SG产生了巨大的兴趣，但SG形成的许多方面仍知之甚少。尽管一些研究表明存在不同的SG亚型和SG样胞质灶，但一般认为不同应力诱导的SG是一致的。在这里，我们研究了SG组装的分子机制，并表征了它们的组成时，诱导的各种应力。我们的数据显示，应力特定的组成，组装和动力学的SG和SG样胞质病灶的差异。使用一组遗传修饰的单倍体人类细胞，我们确定了SG形成上游的应激特异性翻译抑制的分子电路及其与细胞存活的关系。最后，我们的研究表征细胞质应激诱导的病灶相关，但不同的，典型的SG，还介绍了单倍体细胞作为一个有价值的资源，研究RNA颗粒和翻译控制机制。
Cells have developed different mechanisms to respond to stress, including the formation of cytoplasmic foci known as stress granules (SGs). SGs are dynamic and formed as a result of stress-induced inhibition of translation. Despite enormous interest in SGs due to their contribution to the pathogenesis of several human diseases, many aspects of SG formation are poorly understood. SGs induced by different stresses are generally assumed to be uniform, although some studies suggest that different SG subtypes and SG-like cytoplasmic foci exist. Here, we investigated the molecular mechanisms of SG assembly and characterized their composition when induced by various stresses. Our data revealed stress-specific differences in composition, assembly and dynamics of SGs and SGlike cytoplasmic foci. Using a set of genetically modified haploid human cells, we determined the molecular circuitry of stress-specific translation inhibition upstream of SG formation and its relation to cell survival. Finally, our studies characterize cytoplasmic stress-induced foci related to, but distinct from, canonical SGs, and also introduce haploid cells as a valuable resource to study RNA granules and translation control mechanisms.