Aulas Anaïs, Fay Marta M, Lyons Shawn M, Achorn Christopher A, Kedersha Nancy, Anderson Paul, Ivanov Pavel
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
J Cell Sci. 2017 Mar 1;130(5):927-937. doi: 10.1242/jcs.199240. Epub 2017 Jan 17.
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 SG-like 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.
细胞已发展出不同的机制来应对压力，包括形成被称为应激颗粒（SGs）的细胞质聚集体。SGs是动态的，由应激诱导的翻译抑制形成。尽管由于SGs在几种人类疾病发病机制中的作用而备受关注，但SG形成的许多方面仍知之甚少。不同应激诱导的SGs通常被认为是均匀的，尽管一些研究表明存在不同的SG亚型和类SG细胞质聚集体。在这里，我们研究了SG组装的分子机制，并对各种应激诱导下它们的组成进行了表征。我们的数据揭示了SGs和类SG细胞质聚集体在组成、组装和动态方面的应激特异性差异。使用一组基因改造的单倍体人类细胞，我们确定了SG形成上游应激特异性翻译抑制的分子回路及其与细胞存活的关系。最后，我们的研究表征了与经典SGs相关但又不同的细胞质应激诱导聚集体，并将单倍体细胞作为研究RNA颗粒和翻译控制机制的宝贵资源引入。
