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Integrated multi-omics reveals common properties underlying stress granule and P-body formation
bioRxiv - Biochemistry Pub Date : 2020-05-19 , DOI: 10.1101/2020.05.18.102517
Christopher J. Kershaw , Michael G. Nelson , Jennifer Lui , Christian P. Bates , Martin D. Jennings , Simon J. Hubbard , Mark P. Ashe , Chris M. Grant

Non-membrane-bound compartments such as P-bodies (PBs) and stress granules (SGs) play important roles in the regulation of gene expression following environmental stresses. We have systematically determined the protein and mRNA composition of PBs and SGs formed in response to a common stress condition imposed by glucose depletion. We find that high molecular weight (HMW) complexes exist prior to glucose depletion that may act as seeds for the further condensation of proteins forming mature PBs and SGs. Both before and after glucose depletion, these HMW complexes are enriched for proteins containing low complexity and RNA binding domains. The mRNA content of these HMW complexes is enriched for long, structured mRNAs that become more poorly translated following glucose depletion. Many proteins and mRNAs are shared between PBs and SGs including several multivalent RNA binding proteins that may promote condensate interactions during liquid-liquid phase separation. Even where the precise identity of mRNAs and proteins localizing to PBs and SGs is distinct, the mRNAs and proteins share common biophysical and chemical features that likely trigger their phase separation.

中文翻译:

集成的多组学揭示了应力颗粒和P体形成的共同属性

非膜结合区室(例如P体(PBs)和应激颗粒(SGs​​))在环境胁迫后的基因表达调控中起重要作用。我们已经系统地确定了响应于葡萄糖耗竭引起的常见应激条件而形成的PB和SG的蛋白质和mRNA组成。我们发现葡萄糖耗尽之前存在高分子量(HMW)复合物,它可能充当种子进一步凝结形成成熟PB和SG的蛋白质。在葡萄糖耗尽之前和之后,这些HMW复合物都富含低复杂性和RNA结合域的蛋白质。这些HMW复合物的mRNA含量丰富了较长的结构化mRNA,这些葡萄糖在葡萄糖耗尽后翻译变得更差。PB和SG之间共享许多蛋白质和mRNA,包括几种多价RNA结合蛋白,这些蛋白可能会在液-液相分离过程中促进冷凝物相互作用。即使在精确定位于PB和SG的mRNA和蛋白质的位置完全不同的情况下,这些mRNA和蛋白质也具有共同的生物物理和化学特征,可能触发它们的相分离。
更新日期:2020-05-19
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