Biology subjects

Carrasco, J.

Publications and source records attributed to Carrasco, J..

5 recordsLinked to original sources

bioRxiv2026

Regulation of protein abundance in neurons by selective translation of 3'UTR isoforms

The precise regulation of protein synthesis is essential for cellular function and survival. In particular, in neurons, dysregulated mRNA translation is linked to impaired memory formation and is a hallmark of neurodegenerative diseases. Neurons are characterized by tissue-specific, long 3' untranslated regions (3'UTRs); in this study, we demonstrate that mRNA isoforms with these neuronal 3'UTRs are less efficiently translated than their short counterparts in Drosophila and mammalian brains. 3'UTR-dependent translation is based on a negative feedback mechanism centered around the two neural-enriched proteins ELAV and Pumilio. The long elav 3'UTR inhibits production of the neuronal ELAV protein, which in turn mediates 3'UTR extension of hundreds of neuronal genes. Those long 3'UTR isoforms are preferentially bound and translationally inhibited by Pumilio. The regulatory loop maintains optimal neuronal 3'UTR and protein levels in conditions of genetic and environmental perturbations; its disruption reduces animal viability and lowers stress resilience, and causes severe developmental phenotypes in flies and in human brain organoids. We propose 3'UTR-mediated translational control as an evolutionarily conserved mechanism for the maintenance of cell-type-specific proteostasis.

molecular biology↗

bioRxiv2025

Biocontrol against fungal mycoparasites driven by Bacillus velezensis strains from a mushroom crop microcosm

1.The cultivation of button mushroom (Agaricus bisporus) requires the design of tailor-made substrates that nourish the crop and promote morphology changes from mycelium to basidiome. The agronomic stages of mushroom development are also influenced by the microbiota present in the mushroom crop microcosm, which may have a beneficial impact on mushroom growth, development and quality, or a detrimental impact through reduction of yield or quality as parasites, competitors or disease vectors in mushroom crops. In this report we describe the isolation of multiple strains of Bacillus velezensis from mushroom casing material and basidiomes that show antifungal activity towards major mushroom mycoparasites, along with further characterization of their mode of action. Full genomes of B. velezensis CM5, CM19, CM35, EM5 and EM39 were sequenced and annotated, which together with metabolic profiling of specialised metabolites produced by CM5, CM19 and CM35 suggested that the antifungal activity of these strains is linked to the production of the lipopeptide fengycin. However, in crop trials, these strains did not increase mushroom yield or provide significant control of the mushroom parasite Lecanicillium fungicola. Genomic and analytical tools were designed and used to evaluate B. velezensis persistence in casing when the selected strains were artificially applied. B. velezensis population levels decreased significantly after application, potentially contributing to the lack of biocontrol activity observed in crop trials. 3. Key PointsO_LIB. velezensis strains isolated from peat-based microcosms are shown to have significant inhibitory effects against major fungal parasites of mushrooms in vitro. C_LIO_LIThrough full genome sequencing and metabolic profiling using LC-HRMS, the antifungal activity is correlated with the production of lipopeptides, particularly fengycin analogues. C_LIO_LIIn trials using button mushroom crops artificially infected with Lecanicillium fungicola, the causal agent of dry bubble, treatment of casing material with these strains did not significantly limit dry bubble disease or increase yield. C_LIO_LIThe persistence of strains in crop when artificially applied showed significant decreases after application on casing, potentially contributing to the lack of biocontrol activity. C_LI

microbiology↗

bioRxiv2024

Pumilio differentially binds to mRNA 3' UTR isoforms to regulate localization of synaptic proteins

In neuronal cells, the regulation of RNA is crucial for the spatiotemporal control of gene expression, but how the correct localization, levels, and function of synaptic proteins are achieved is not well understood. In this study, we globally investigate the role of alternative 3 UTRs in regulating RNA localization in the synaptic regions of the Drosophila brain. We identify direct mRNA targets of the translational repressor Pumilio, finding that mRNAs bound by Pumilio encode proteins enriched in synaptosomes. Pumilio differentially binds to RNA isoforms of the same gene, favoring long, neuronal 3 UTRs. These longer 3 UTRs tend to remain in the neuronal soma, whereas shorter UTR isoforms localize to the synapse. In cultured pumilio mutant neurons, severe axon outgrowth defects were accompanied by mRNA isoform mislocalization, and proteins encoded by these Pumilio targets displayed excessive abundance at synaptic boutons. Our study identifies an important and widespread mechanism for the spatiotemporal regulation of protein function in neurons.

genomics↗

bioRxiv2024

ELAV mediates circular RNA biogenesis in neurons

Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally (>75%) depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In brain tissue, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.

molecular biology↗

bioRxiv2021

RUSBoost: A suitable species distribution method for imbalanced records of presence and absence. A case study of twenty-five species of Iberian bats

O_LITraditional Species Distribution Models (SDMs) may not be appropriate when examples of one class (e.g. absence or pseudo-absences) greatly outnumber examples of the other class (e.g. presences or observations), because they tend to favor the learning of observations more frequently. C_LIO_LIWe present an ensemble method called Random UnderSampling and Boosting (RUSBoost), which was designed to address the case where the number of presence and absence records are imbalanced, and we opened the "black-box" of the algorithm to interpret its results and applicability in ecology. C_LIO_LIWe applied our methodology to a case study of twenty-five species of bats from the Iberian Peninsula and we build a RUSBoost model for each species. Furthermore, in order to improve to build tighter models, we optimized their hyperparameters using Bayesian Optimization. In particular, we implemented a objective function that represents the cross-validation loss: [Formula], with [Formula] representing the hyper-parameters Maximum Number of Splits, Number of Learners and Learning Rate. C_LIO_LIThe models reached average values for Area Under the ROC Curve (AUC), specificity, sensitivity, and overall accuracy of 0.84 {+/-} 0.05%, 79.5 {+/-} 4.87%, 74.9 {+/-} 6.05%, and 78.8 {+/-} 5.0%, respectively. We also obtained values of variable importance and we analyzed the relationships between explanatory variables and bat presence probability. C_LIO_LIThe results of our study showed that RUSBoost could be a useful tool to develop SDMs with good performance when the presence/absence databases are imbalanced. The application of this algorithm could improve the prediction of SDMs and help in conservation biology and management. C_LI

ecology↗