Biology subjects

Rosa, H.

Publications and source records attributed to Rosa, H..

4 recordsLinked to original sources

bioRxiv2026

A Novel Eukaryotic Ribosome Factor Enables Translation Restart Following Cellular Dormancy

Dormancy is a survival strategy employed by all domains of life to withstand prolonged nutrient deprivation and environmental stress that is marked by a global shutdown of protein synthesis. However, the molecular mechanisms driving ribosome inactivation and reactivation during and after dormancy in eukaryotes remain poorly understood. Here, we identify SNOR, a novel SBDS-like ribosome-associated factor in Schizosaccharomyces pombe, that is upregulated and associates with ribosomes during induced dormancy triggered by glucose depletion. SNOR contributes to protein synthesis repression by binding the ribosome to probe the peptidyl transferase center (PTC), block tRNA-binding sites, and cap the polypeptide exit tunnel (PET). Importantly, we show that SNOR is essential for the restart of protein synthesis upon glucose reintroduction and exit from dormancy. SNOR is evolutionarily conserved and specifically upregulated in response to glucose stress in fungi. These findings reveal a previously unrecognized ribosome-associated factor that links glucose stress and cellular dormancy to surveillance of protein synthesis and highlight the power of in situ structural biology to uncover stress-responsive regulators of translation.

biophysics↗

bioRxiv2026

An Advanced Mobile Laboratory to enable field-based microbial ecology and cell biology across scales

Microbial biodiversity is central to ecosystem function, yet mechanistic insights into the cell biology of environmental organisms remain limited. The underlying challenges are twofold: most microbes remain uncultivable, and a persistent gap exists between field sampling and laboratory analyses. Here, we introduce the Advanced Mobile Laboratory (AML), a field-deployable platform that integrates confocal microscopy, image-enabled cell sorting, and cryo-preparation for expansion and electron microscopy. This setup enables immediate, standardized processing and analysis of environmental communities directly at the sampling site. We demonstrate its capability using marine eukaryotic plankton, showing how the AML enables multiscale investigations, from live imaging of natural communities to enabling ultrastructural and single-cell omics analyses, while minimizing sample degradation and enabling on-site experimentation. By bringing high-end sample preparation and analytical capacity into the field, the AML enables studying life in its natural context to mechanistically understand lifes diversity in the environment.

cell biology↗

bioRxiv2023

Hibernating ribosomes tether to mitochondria as an adaptive response to cellular stress during glucose depletion

Cell survival under nutrient-deprived conditions relies on cells ability to adapt their organelles and to rewire their metabolic pathways. In the fission yeast Schizosaccharomyces pombe, nutrient depletion is an unfavorable condition for protein synthesis and triggers a response characterized by mitochondrial fragmentation and the sequestration of cytosolic ribosomes on mitochondria. The molecular mechanism underlying ribosomal sequestration remains elusive. In this study, we performed time-lapse in situ cryo-electron tomography and cryo-electron microscopy complemented by biochemical experiments to elucidate the molecular details of this adaptive response. Our analysis indicate that upon glucose depletion protein synthesis is halted, causing ribosomes to enter an inactive state characterized by a conformational change that obstructs the peptidyl transferase center. Our in situ experiments reveal the presence of oligomeric arrays of hibernating ribosomes tethered to the mitochondrial surface. Surprisingly, ribosomes bind to the outer mitochondrial membrane via the small ribosomal subunit, an interaction facilitated by the ribosomal protein RACK1-orthologue Cpc2. Our experiments show that ribosome tethering is important for cell survival under glucose depletion conditions. This study broadens our understanding of the cellular adaptations triggered by nutrient scarcity and the underlying molecular mechanisms that regulate cell quiescence.

molecular biology↗

bioRxiv2020

A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral main protease is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. Although several mechanisms of self-cleavage had been proposed for SARS-CoV, the lack of structural information for each step is a setback to the understanding of this process. Herein, we used X-ray crystallography to characterize an immature form of the main protease, which revealed major conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis-cleavage of N-terminal residues within the dimer, leading to the mature active site. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the main protease bound to its endogenous N and C-terminal residues during the formation of the tetramer. This quaternary form is also present in solution, suggesting a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during maturation, which can guide the development of new inhibitors targeting its intermediary states.

biochemistry↗