Biology subjects

Jacquel, B.

Publications and source records attributed to Jacquel, B..

3 recordsLinked to original sources

bioRxiv2021

Nuclear Pore Complex Acetylation Regulates mRNA Export and Cell Cycle Commitment in Budding Yeast

Nuclear pore complexes (NPCs) mediate communication between the nucleus and the cytoplasm and regulate gene expression by interacting with transcription and mRNA export factors. Lysine acetyl-transferases (KATs) promote transcription through acetylation of chromatin-associated proteins. We find that Esa1, the KAT subunit of the yeast NuA4 complex, also acetylates the nuclear pore basket component Nup60 to promote mRNA export. Acetylation of Nup60 recruits to the nuclear basket the mRNA export factor Sac3, the scaffolding subunit of the Transcription and Export 2 (TREX-2) complex. Esa1-dependent nuclear export of mRNAs promotes entry into S phase, and is inhibited by the Hos3 deacetylase in G1 daughter cells to restrain their premature commitment to a new cell division cycle. This mechanism also inhibits expression of the nutrient-regulated GAL1 gene specifically in daughter cells. These results reveal how acetylation contributes to the functional plasticity of NPCs in specific cell types, and demonstrate how the evolutionarily conserved NuA4 complex regulates gene expression dually at the level of transcription and mRNA export, by modifying the nucleoplasmic entrance to nuclear pores.

cell biology↗

bioRxiv2021

A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide

The physiological adaptation to environmental stress involves complex molecular responses leading to separate cellular fates aimed at maximizing fitness: either cells can maintain proliferation by degrading the effects of the stressor (i.e. resistance), or they focus on ensuring cell survival (i.e. tolerance), even at the expense of proliferation. These strategies are complementary, yet whether they are coordinated to ensure an optimal physiological stress response remains unknown. Here, we used microfluidics and live cell imaging to explore the genetic basis of the interplay between resistance and tolerance during the response to hydrogen peroxide (H2O2) in budding yeast. Our analysis unraveled that the deletion of zwf1{Delta}, which is responsible for NADPH synthesis via the PPP pathway, led to a decrease in resistance that was counterbalanced by an unexpected exacerbation of tolerance to H2O2. This trade-off between stress resistance and stress tolerance was further characterized using both genetic and environmental interventions, and we confirmed that it was conserved in bacteria. Our results support a model in which redox signaling triggers the switch to a nutrients-dependent non-proliferative tolerant state via inhibition of protein kinase A when the H2O2 homeostatic response is overwhelmed. Our framework could help develop synergistic therapies that target mechanisms driving both resistance and tolerance to prevent drug escape mechanisms and disease relapse.

cell biology↗

bioRxiv2020

pH fluctuations drive waves of stereotypical cellular reorganizations during entry into quiescence

The life cycle of microorganisms is associated with dynamic metabolic transitions and complex cellular responses. In yeast, how metabolic signals control the progressive choreography of structural reorganizations observed in quiescent cells during a natural life cycle remains unclear. We have developed an integrated microfluidic device to address this question, enabling continuous single-cell tracking in a batch culture experiencing unperturbed nutrient exhaustion to unravel the coordination between metabolic and structural transitions within cells. Our technique reveals an abrupt fate divergence in the population, whereby a fraction of cells is unable to transition to respiratory metabolism and undergoes a reversible entry into a quiescence-like state leading to premature cell death. Further observations reveal that non-monotonous internal pH fluctuations in respiration-competent cells orchestrate the successive waves of protein super-assemblies formation that accompany the entry into a bona fide quiescent state. This ultimately leads to an abrupt cytosolic glass transition that occurs stochastically long after proliferation cessation. This new experimental framework provides a unique way to track single-cell fate dynamics over a long timescale in a population of cells that continuously modify their ecological niche.

cell biology↗