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Delineating the role of stress granules in senescent cells exposed to external assaults

Authors
Publisher
McGill University
Publication Date
Keywords
  • Cell Aging -- Physiology.
  • Cytoplasmic Granules -- Physiology.
  • Oxidative Stress -- Physiology.
  • Arsenites -- Toxicity.
  • Cyclin-Dependent Kinase Inhibitor P21 -- Metabolism.
Disciplines
  • Biology
  • Ecology
  • Geography

Abstract

As we age, our ability to cope with a variety of stresses significantly decreases. One of the features of an ageing organism is the dramatic increase in the number of cells arrested in the G1 phase, a process known as senescence. It is well established that the senescence phenotype leads to a change in the way cells respond to stress. However, the molecular mechanisms by which these cells cope and/or respond to a variety of environmental challenges remain unknown. In general, cells respond to stress by engaging a variety of mechanisms; one of them is the assembly of cytoplasmic foci known as stress granules (SGs). These entities are considered as part of the survival pathways that are activated at the beginning of any stress to protect key cellular elements which allow a quick recovery if the stress is rapidly removed. However, we do not know whether SGs formation is activated during senescence. In this study, we investigated the formation and the role of SGs in senescent cells exposed to various stresses. We demonstrated that while SGs can assemble in response to oxidative stress (OS) during all the steps leading to senescence activation, their number significantly increases at late stage of senescence. This increase correlates with a rapid decrease in the expression of the cyclin kinase inhibitor p21, one of the main players in the activation of the senescence phenotype. Although the OS-induced recruitment of p21 mRNA to SGs correlates with a significant increase in its half-life, this translocation interferes with p21 translation only at late senescence. This translation inhibition could be explained by the co-recruitment of CUGBP1, a known translation activator during senescence of p21, and p21 mRNA to SGs. Therefore, our data suggest that SGs formation and the reduction in p21 protein levels represent two main events through which senescent cells respond to stress conditions.

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