Biology subjects

Padilla, G.

Publications and source records attributed to Padilla, G..

3 recordsLinked to original sources

bioRxiv2025

An Nrf2/Yap1-like bZIPprotein drives UV-induced oxidative stress response in a Sporobolomyces yeast with evolutionary conservation

Research backgroundUltraviolet radiation represents a major environmental hazard that damages DNA and promotes oxidative stress in all living organisms. In animals, this stress is counteracted by the Nrf2 signalling pathway, while in yeasts such as Saccharomyces cerevisiae, the Yap1 transcription factor coordinates oxidative stress responses. The extent to which these mechanisms are conserved in UV-tolerant yeasts from the Basidiomycota lineage remains poorly understood. Experimental approachWe investigated the stress response of a UV-tolerant Sporobolomyces sp. isolates exposed to long-term ultraviolet-B irradiation. Yeast survival and antioxidant capacity were assessed, followed by proteome-wide quantification of protein expression using tandem mass tag labelling and multidimensional protein identification technology. Proteins were annotated for biological function through gene ontology and pathway analyses to identify stress-related factors and transcriptional regulators. Results and conclusionsThe LEV-2 Sporobolomyces yeast isolate displayed remarkable survival under conditions lethal to S. cerevisiae and showed induction of antioxidant activity during prolonged exposure. Proteomic profiling revealed large-scale adjustments in protein expression, including the upregulation of enzymes involved in antioxidant biosynthesis, enzymatic antioxidants, DNA repair proteins, heat shock proteins, and multiple signalling pathways. Importantly, several basic leucine zipper proteins with similarity to animal Nrf2 and yeast Yap1 were detected, with one factor showing a distinct induction in response to ultraviolet stress. These findings suggest that the oxidative stress response of Sporobolomyces is mediated by conserved regulatory modules comparable to those of both yeasts and animals, highlighting the evolutionary conservation of stress adaptation mechanisms. Novelty and scientific contributionThis work provides the first proteome-level description of the ultraviolet stress response in a Basidiomycota yeast. It demonstrates that bZIP transcription factors drive a complex antioxidant and repair programme in Sporobolomyces, functionally reminiscent of the animal Nrf2 pathway. The results support the view that fundamental oxidative stress responses arose early in eukaryotic evolution and have been preserved across distant fungal and animal lineages.

microbiology↗

bioRxiv2024

Characterization of a marine bacteria through a novel metabologenomics approach

Exploiting microbial natural products is a key pursuit of the bioactive compound discovery field. Recent advances in modern analytical techniques have increased the volume of microbial genomes and their encoded biosynthetic products measured by mass spectrometry-based metabolomics. However, connecting multi-omics data to uncover metabolic processes of interest is still challenging. This results in a large portion of genes and metabolites remaining unannotated. Further exacerbating the annotation challenge, databases and tools for annotation and omics integration are scattered, requiring complex computations to annotate and integrate omics datasets. Here we performed a two-way integrative analysis combining genomics and metabolomics data to describe a new approach to characterize the marine bacterial isolate BRA006 and to explore its biosynthetic gene cluster (BGC) content as well as the bioactive compounds detected by metabolomics. We described BRA006 genomic content and structure by comparing Illumina and Oxford Nanopore MinION sequencing approaches. Digital DNA:DNA hybridization (dDDH) taxonomically assigned BRA006 as a potential new species of the Micromonospora genus. Starting from LC-ESI(+)-HRMS/MS data, and mapping the annotated enzymes and metabolites belonging to the same pathways, our integrative analysis allowed us to correlate the compound Brevianamide F to a new BGC, previously assigned to other function.

biochemistry↗

bioRxiv2023

Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains

RNA-binding proteins with prion-like domains, such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs (24-48 nucleotides) that prevent FUS fibrillization by promoting liquid phases, and distinct short RNAs that prevent and, remarkably, reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. Importantly, we define a short RNA that dissolves aberrant cytoplasmic FUS condensates, restores nuclear FUS, and mitigates FUS proteotoxicity in optogenetic models and human motor neurons. Another short RNA dissolves aberrant cytoplasmic TDP-43 condensates, restores nuclear TDP-43, and mitigates TDP-43 proteotoxicity. Since short RNAs can be effectively delivered to the human brain, these oligonucleotides could have therapeutic utility for ALS/FTD and related disorders.

biochemistry↗