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Open AccessJournal ArticleDOI

Mechanistic insights into mammalian stress granule dynamics

TLDR
Panas et al. review the mechanisms that control the dynamic formation and disassembly of RNA stress granules and highlight the importance of knowing the carrier and removal status of canine coronavirus.
Abstract
The accumulation of stalled translation preinitiation complexes (PICs) mediates the condensation of stress granules (SGs). Interactions between prion-related domains and intrinsically disordered protein regions found in SG-nucleating proteins promote the condensation of ribonucleoproteins into SGs. We propose that PIC components, especially 40S ribosomes and mRNA, recruit nucleators that trigger SG condensation. With resolution of stress, translation reinitiation reverses this process and SGs disassemble. By cooperatively modulating the assembly and disassembly of SGs, ribonucleoprotein condensation can influence the survival and recovery of cells exposed to unfavorable environmental conditions.

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Citations
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Journal ArticleDOI

G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules

TL;DR: It is shown that SGs assemble through liquid-liquid phase separation (LLPS) arising from interactions distributed unevenly across a core protein-RNA interaction network, and that interplay between three distinct intrinsically disordered regions (IDRs) in G3BP1 regulates its intrinsic propensity for LLPS.
Journal ArticleDOI

The Stress Granule Transcriptome Reveals Principles of mRNA Accumulation in Stress Granules

TL;DR: The results suggest that stress granules may not represent a specific biological program of messenger ribonucleoprotein (mRNP) assembly, but instead form by condensation of nontranslating mRNPs in proportion to their length and lack of association with ribosomes.
Journal ArticleDOI

Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing.

TL;DR: A review of the role of biomolecular condensates in ageing and disease can be found in this paper, where the authors discuss how cellular stress, ageing-related loss of homeostasis and a decline in protein quality control may contribute to the formation of aberrant, disease-causing condensate.
References
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Journal ArticleDOI

Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets

TL;DR: Recent advances in understanding of the molecular structures and biochemical functions of the translation initiation machinery are described and key strategies that mediate general or gene-specific translational control are summarized, particularly in mammalian systems.
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Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.

TL;DR: Many proteins that lack intrinsic globular structure under physiological conditions have now been recognized, and it appears likely that their rapid turnover, aided by their unstructured nature in the unbound state, provides a level of control that allows rapid and accurate responses of the cell to changing environmental conditions.
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The mechanism of eukaryotic translation initiation and principles of its regulation

TL;DR: This work has provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).
Journal ArticleDOI

Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation

TL;DR: It is shown that P granules exhibit liquid-like behaviors, including fusion, dripping, and wetting, which is used to estimate their viscosity and surface tension, and reflects a classic phase transition, in which polarity proteins vary the condensation point across the cell.
Journal ArticleDOI

Intrinsically unstructured proteins.

TL;DR: In this review, recent findings are surveyed to illustrate that this novel but rapidly advancing field has reached a point where proteins can be comprehensively classified on the basis of structure and function.
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