Stress granules display bistable dynamics modulated by Cdk

Stress granules are biomolecular condensates of nontranslating mRNAs and diverse proteins. Yahya et al. uncover a mutual-inhibition system between stress granules and the cyclin-dependent kinase, the key cell cycle regulator, whereby Cdks regulate SG dynamics and SGs contribute to inhibiting cyclin transcript translation.

Stress granules are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge on their regulation and functional relevance is still incipient. Here we describe a mutual-inhibition interplay between stress granules and Cdc28, the budding yeast Cdk. Amongst Cdc28 interactors acting as negative modulators of Start we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdks subjugate SG dynamics to a conserved hysteretic switch.

Yahya G, Pérez AP, Mendoza MB, Parisi E, Moreno DF, Artés MH, Gallego C, Aldea M.
Stress granules display bistable dynamics modulated by Cdk.
J Cell Biol. 2021 Mar 1;220(3):e202005102. doi: 10.1083/jcb.202005102.

Mutual inhibitory roles of Cdk and SGs create a bistable memory system to prevent SG formation at low stress and, once SGs are formed, sustain their presence until normal conditions are entirely restored.