Biology subjects

Parisi, E.

Publications and source records attributed to Parisi, E..

2 recordsLinked to original sources

bioRxiv2020

Stress granules display bistable dynamics modulated by Cdk

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.

cell biology↗

bioRxiv2018

The chaperone-client network subordinates cell-cycle entry to growth and stress

The precise coordination of growth and proliferation has a universal prevalence in cell homeostasis. As a prominent property, cell size is modulated by the coordination between these processes in bacterial, yeast and mammalian cells, but the underlying molecular mechanisms are largely unknown. Here we show that multifunctional chaperone systems play a concerted and limiting role in cell-cycle entry, specifically driving nuclear accumulation of the G1 Cdk-cyclin complex. Based on these findings, we establish and test a molecular competition model that recapitulates cell-cycle-entry dependence on growth rate. As key predictions at a single-cell level, we show that availability of the Ydj1 chaperone and nuclear accumulation of the G1 cyclin Cln3 are inversely dependent on growth rate and readily respond to changes in protein synthesis and stress conditions that alter protein folding requirements. Thus, chaperone workload would subordinate Start to the biosynthetic machinery and dynamically adjust proliferation to the growth potential of the cell.

molecular biology↗