Biology subjects

Pujol, A.

Publications and source records attributed to Pujol, A..

5 recordsLinked to original sources

bioRxiv2026

HERVs as building blocks of RNA regulatory architecture in the human genome

Human endogenous retroviruses (HERVs) comprise nearly 8% of the human genome and have contributed extensively to gene regulatory evolution. However, their roles in RNA-centered regulatory processes remain poorly characterized. Here, we present a genome-wide annotation of RNA regulatory features embedded within HERV internal regions and long terminal repeats (LTRs), revealing that HERV sequences act as pervasive components of the human transcriptome. Systematic analysis of RNA-binding protein (RBP) motifs uncovers structured, family-specific regulatory architectures, with distinct RBP signatures distinguishing major HERV subfamilies. Notably, HERVH elements are enriched for RBPs associated with developmentally regulated RNA processing, whereas HERVK (HML-2) elements preferentially harbor motifs linked to canonical splicing and mRNA maturation. Integration with gene annotations reveals widespread incorporation of HERV sequences into transcript structures, including more than 4,000 long non-coding RNAs. Conserved retroviral protein domains within predicted open reading frames are strongly enriched in terminal exons and 3' untranslated regions, consistent with potential micropeptide-encoding capacity. In addition, we identify a subclass of lncRNAs largely composed of HERV sequence, indicating that endogenous retroviral loci have been extensively captured within annotated transcripts. Finally, we detect more than 6,500 antisense LTR insertions in transcript termini, defining widespread SPARCS-like (stimulated 3 prime antisense retroviral coding sequences) configurations with potential for double-stranded RNA formation and preferential association with immune-related genes. Together, these results establish HERV sequences as a pervasive layer of RNA regulatory potential embedded within human transcripts, highlighting previously underappreciated roles in post-transcriptional gene regulation.

genomics↗

bioRxiv2026

Regulatory Features and Functional Specialization of Human Endogenous Retroviral LTRs: A Genome-Wide Annotation and Analysis via HERVarium

Human endogenous retroviruses (HERVs), remnants of ancient retroviral infections, account for over 8% of the human genome and remain an underexplored source of cis-regulatory elements and protein-coding remnants. Here we present HERVarium, an integrated and interactive database that provides access to systematic annotations of the protein-domain architecture of internal HERV regions and the regulatory landscape of their LTRs across the human genome. Building on our previous catalog of conserved retroviral domains, we classified over 400,000 LTRs by structure (solo, 5', or 3' LTR), proximity to transcription start sites (TSS), potential transcription-factor binding-motif (TFBM) burden, and computationally reconstructed their canonical U3-R-U5 substructure, revealing that two-thirds retain recognizable segmentation, particularly those adjacent to conserved internal domains. LTRs flanking internal regions with conserved Gag, Pol, or Env domains tend to be longer and richer in motifs, suggesting coordinated maintenance of coding and regulatory potential. Conversely, solo LTRs positioned at gene TSSs exhibit promoter-like architectures enriched in motifs for developmental and proliferative regulators, while selectively lacking motifs associated with neuronal differentiation. Some 5' LTRs at lncRNA TSSs also flank conserved retroviral domains, indicating that certain lncRNAs may derive from transcriptionally active, structurally intact HERV loci. HERVarium provides a comprehensive, interactive resource to explore and download these annotations at single-locus resolution.

genomics↗

bioRxiv2022

Role of UCP2 in the energy metabolism of the cancer cell line A549

The uncoupling protein UCP2 is a mitochondrial carrier whose transport activity remains controversial. The physiological contexts in which UCP2 is expressed have led to the assumption that, like UCP1, it uncouples oxidative phosphorylation and as a result it lowers the generation of reactive oxygen species. Other reports have involved UCP2 in the Warburg effect and results showing that UCP2 catalyzes the export of matrix C4 metabolites to facilitate glutamine utilization, suggests that the carrier could be involved in the metabolic adaptations required for cell proliferation. We have examined the role of UCP2 in the energy metabolism of the lung adenocarcinoma cell line A549 and show that UCP2 silencing decreased the basal rate of respiration although this inhibition was not compensated by an increase in glycolysis. Silencing did not lead to changes in proton leakage, as determined from the rate of respiration in the absence of ATP synthesis, or changes in the rate of formation of reactive oxygen species. The decrease in energy metabolism did not alter the cellular energy charge. The decreased cell proliferation observed in UCP2-silenced cells would explain the decreased cellular ATP demand. We conclude that UCP2 does not operate as an uncoupling protein while our results are consistent with its activity as a C4-metabolite carrier involved in the metabolic adaptations of proliferating cells. HighlightsO_LIUCP2 silencing decreases respiration without a compensatory increase in aerobic glycolysis C_LIO_LIATP levels remain unchanged despite the reduction in energy metabolism C_LIO_LIUCP2 silencing decreases cell proliferation that could explain the decrease in energy demand C_LIO_LIUCP2 silencing does not change the proton leakage rate C_LIO_LIData support the proposed involvement of UCP2 in the Warburg effect C_LI

biochemistry↗

bioRxiv2021

The human sperm basal body is a complex centrosome important for embryo pre-implantation development

The mechanism of conversion of the human sperm basal body to a centrosome after fertilization, and its role in supporting human early embryogenesis has not been directly addressed so far. Using proteomics and immunofluorescence studies we show here that the human zygote inherits a basal body enriched with centrosomal proteins from the sperm, establishing the first functional centrosome of the new organism. Injection of human sperm tails containing the basal body into human oocytes followed by parthenogenetically activation, showed that the centrosome contributes to the robustness of the early cell divisions, increasing the probability of parthenotes reaching the compaction stage. In the absence of the sperm-derived centrosome, pericentriolar (PCM) components stored in the oocyte can form de novo structures after genome activation, suggesting a tight PCM expression control in zygotes. Our results reveal that the sperm basal body is a complex organelle which converts to a centrosome after fertilization, ensuring the early steps of embryogenesis and successful compaction. However, more experiments are needed to elucidate the exact molecular mechanisms of centrosome inheritance in humans.

developmental biology↗

bioRxiv2019

TPMS technology to infer biomarkers of macular degeneration prognosis in in silico simulated prototype-patients under the study of heart failure treatment with sacubitril and valsartan

Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of drug(s) in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalised medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. This is achieved by (1) modelling the responses in human with an accurate description of the protein networks and (2) applying a Multilayer Perceptron-like and sampling method strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a range of mechanism of action models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their relationship with macular degeneration (a common/recurrent adverse effect). We found that a lower response in terms of heart failure treatment is more associated to macular degeneration development, although good response mechanisms can also associate to the adverse effect. A set of 30 potential biomarkers are proposed to identify mechanisms (or patients) more prone to suffering macular degeneration when presenting good heart failure response. As each molecular mechanism can be particular not only of cells but also individuals, we conclude that the study of the collection of models generated using TPMS technology can be used to detect adverse effects personalized to patients.

bioinformatics↗