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Title: Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response

Abstract

In eukaryotic cells, diverse stresses trigger coalescence of RNA-binding proteins into stress granules. In vitro, stress-granule-associated proteins can demix to form liquids, hydrogels, and other assemblies lacking fixed stoichiometry. Observing these phenomena has generally required conditions far removed from physiological stresses. We show that poly(A)-binding protein (Pab1 in yeast), a defining marker of stress granules, phase separates and forms hydrogels in vitro upon exposure to physiological stress conditions. Other RNA-binding proteins depend upon low-complexity regions (LCRs) or RNA for phase separation, whereas Pab1’s LCR is not required for demixing, and RNA inhibits it. Based on unique evolutionary patterns, we create LCR mutations, which systematically tune its biophysical properties and Pab1 phase separation in vitro and in vivo. Mutations that impede phase separation reduce organism fitness during prolonged stress. Poly(A)-binding protein thus acts as a physiological stress sensor, exploiting phase separation to precisely mark stress onset, a broadly generalizable mechanism.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1400296
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell; Journal Volume: 168; Journal Issue: 6
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Riback, Joshua A., Katanski, Christopher D., Kear-Scott, Jamie L., Pilipenko, Evgeny V., Rojek, Alexandra E., Sosnick, Tobin R., and Drummond, D. Allan. Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response. United States: N. p., 2017. Web. doi:10.1016/j.cell.2017.02.027.
Riback, Joshua A., Katanski, Christopher D., Kear-Scott, Jamie L., Pilipenko, Evgeny V., Rojek, Alexandra E., Sosnick, Tobin R., & Drummond, D. Allan. Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response. United States. doi:10.1016/j.cell.2017.02.027.
Riback, Joshua A., Katanski, Christopher D., Kear-Scott, Jamie L., Pilipenko, Evgeny V., Rojek, Alexandra E., Sosnick, Tobin R., and Drummond, D. Allan. Wed . "Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response". United States. doi:10.1016/j.cell.2017.02.027.
@article{osti_1400296,
title = {Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response},
author = {Riback, Joshua A. and Katanski, Christopher D. and Kear-Scott, Jamie L. and Pilipenko, Evgeny V. and Rojek, Alexandra E. and Sosnick, Tobin R. and Drummond, D. Allan},
abstractNote = {In eukaryotic cells, diverse stresses trigger coalescence of RNA-binding proteins into stress granules. In vitro, stress-granule-associated proteins can demix to form liquids, hydrogels, and other assemblies lacking fixed stoichiometry. Observing these phenomena has generally required conditions far removed from physiological stresses. We show that poly(A)-binding protein (Pab1 in yeast), a defining marker of stress granules, phase separates and forms hydrogels in vitro upon exposure to physiological stress conditions. Other RNA-binding proteins depend upon low-complexity regions (LCRs) or RNA for phase separation, whereas Pab1’s LCR is not required for demixing, and RNA inhibits it. Based on unique evolutionary patterns, we create LCR mutations, which systematically tune its biophysical properties and Pab1 phase separation in vitro and in vivo. Mutations that impede phase separation reduce organism fitness during prolonged stress. Poly(A)-binding protein thus acts as a physiological stress sensor, exploiting phase separation to precisely mark stress onset, a broadly generalizable mechanism.},
doi = {10.1016/j.cell.2017.02.027},
journal = {Cell},
number = 6,
volume = 168,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2017},
month = {Wed Mar 01 00:00:00 EST 2017}
}
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