Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change.,Molecular Cell

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Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change.
Molecular Cell ( IF 14.5 ) Pub Date : 2020-08-27 , DOI: 10.1016/j.molcel.2020.08.004
Ameya P Jalihal ₁ , Sethuramasundaram Pitchiaya ₂ , Lanbo Xiao ₃ , Pushpinder Bawa ₄ , Xia Jiang ₄ , Karan Bedi ₅ , Abhijit Parolia ₃ , Marcin Cieslik ₆ , Mats Ljungman ₇ , Arul M Chinnaiyan ₈ , Nils G Walter ₉

Affiliation

Single Molecule Analysis Group, Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA; Cell and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-1055, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA.
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-1055, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-1055, USA.
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-1055, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-1055, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA.
Single Molecule Analysis Group, Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA.

Processing bodies (PBs) and stress granules (SGs) are prominent examples of subcellular, membraneless compartments that are observed under physiological and stress conditions, respectively. We observe that the trimeric PB protein DCP1A rapidly (within ∼10 s) phase-separates in mammalian cells during hyperosmotic stress and dissolves upon isosmotic rescue (over ∼100 s) with minimal effect on cell viability even after multiple cycles of osmotic perturbation. Strikingly, this rapid intracellular hyperosmotic phase separation (HOPS) correlates with the degree of cell volume compression, distinct from SG assembly, and is exhibited broadly by homo-multimeric (valency ≥ 2) proteins across several cell types. Notably, HOPS sequesters pre-mRNA cleavage factor components from actively transcribing genomic loci, providing a mechanism for hyperosmolarity-induced global impairment of transcription termination. Our data suggest that the multimeric proteome rapidly responds to changes in hydration and molecular crowding, revealing an unexpected mode of globally programmed phase separation and sequestration.

中文翻译：

多价蛋白质在渗透池体积变化时快速、可逆地发生相分离。

加工体（PB）和应激颗粒（SG）是分别在生理和应激条件下观察到的亚细胞无膜区室的突出例子。我们观察到，在高渗应激期间，三聚体 PB 蛋白 DCP1A 在哺乳动物细胞中快速（约 10 秒内）相分离，并在等渗救援（超过约 100 秒）时溶解，即使在多次渗透扰动循环后，对细胞活力的影响也很小。引人注目的是，这种快速的细胞内高渗相分离 (HOPS) 与细胞体积压缩程度相关，与 SG 组装不同，并且在多种细胞类型的同源多聚体（效价≥2）蛋白中广泛表现出来。值得注意的是，HOPS 从活跃转录的基因组位点中隔离前 mRNA 裂解因子成分，为高渗透压诱导的转录终止全局损伤提供了一种机制。我们的数据表明，多聚体蛋白质组对水合和分子拥挤的变化迅速做出反应，揭示了一种意想不到的全局编程相分离和隔离模式。

更新日期：2020-09-18

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