Biology subjects

Montserrat-Ayuso, T.

Publications and source records attributed to Montserrat-Ayuso, T..

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↗

bioRxiv2025

Single-Cell Dissection of Immunometabolic Rewiring in the Porcine Ileum during Salmonella Typhimurium Infection

Salmonella Typhimurium is a major zoonotic pathogen, with pigs acting as important subclinical carriers. To explore the specific intestinal immune response at the cellular level, we used Single-cell RNA sequencing (scRNA-seq), enabling detailed analysis of immune cell types and gene expression profiles during infection. In addition to enterocytes, our results revealed the presence of diverse immune populations, including monocytes/macrophages, dendritic cells, innate lymphoid cells (ILCs), thirteen T cell subtypes and five B cell populations were identified, revealing pronounced infection-driven alterations in cellular composition and transcriptional states. Among T cells, naive and follicular CD4+/CD8+ {beta} T cells and NK T cells were expanded, whereas effector CD8+ T cells and CD2- and SELLhi {gamma}{delta} T cells were decreased. B-cell populations shifted toward activated and cycling states, with decreased antibody-secreting, resting, and transitioning cells. Dendritic cells and monocyte/macrophage populations were expanded, and group 3 ILCs and enterocytes were markedly reduced. Pathway analyses revealed robust cell type-specific immunometabolic remodeling, including enhanced protein-folding and stress-adaptive pathways in T and B cells, heightened inflammatory, interferon, and cytokine signaling in myeloid populations, and coordinated metabolic and immune adjustments in epithelial cells, highlighting the complexity of host responses to Salmonella infection. This study provides the first scRNA-seq landscape of the porcine ileum during S. Typhimurium infection, offering insight into host immune cell dynamics and immunometabolic responses.

genomics↗

bioRxiv2025

A Comprehensive Annotation of Conserved Protein Domains in Human Endogenous Retroviruses

Human endogenous retroviruses (HERVs) occupy nearly 8% of the human genome, yet their protein-coding potential remains largely unexplored. HERVs originate from ancestral exogenous retroviruses that infected germline cells and became integrated into the human genome. Like their exogenous counterparts, they typically follow the canonical proviral structure: LTR-gag-pol-env-LTR, where gag, pol, and env encode structural, enzymatic, and envelope proteins, respectively. Here, we present a comprehensive resource annotating conserved retroviral domains across 120,000+ ORFs derived from internal HERV regions. Using a reproducible pipeline based on HMMER and InterProScan, we identified over 17,000 domain hits--primarily from pol genes such as reverse transcriptase, RNase H, and protease--and quantified their structural conservation. Hundreds of domains exceed 95% alignment coverage, revealing a surprising abundance of full-length, retrovirus-like domains in both young and ancient HERV families. While the HERVK subfamily retains the most complete polyprotein architecture--including 13 loci with nearly intact Gag, Pol, and Env domains--many full-length Pol domains are also found in other families such as HERVH, HERVW, and HERVE. Our high-resolution annotations recover conserved catalytic motifs in Pol domains and transmembrane features in Env, enabling fine-grained functional interpretation. All annotations--including BED, FASTA, domain sequences, InterProScan outputs, and transmembrane predictions--are provided as an open resource for functional genomics and HERV expression studies at Zenodo (DOI: https://doi.org/10.5281/zenodo.17129661). This dataset will support downstream analyses of HERV protein expression, immune modulation, and co-option, in diseases and normal physiological conditions.

genomics↗

bioRxiv2024

Revealing the Prevalence of Suboptimal Cells and Organs in Reference Cell Atlases: An Imperative for Enhanced Quality Control

The advent of droplet-based single-cell RNA-sequencing (scRNA-seq) has dramatically increased data throughput, enabling the release of a diverse array of tissue cell atlases to the public. However, we will show that prominent initiatives such as the Human Cell Atlas, Tabula Muris, and Tabula Sapiens contain a significant amount of contamination products (frequently affecting the whole organ) in their data portals due to suboptimal quality filtering. Our work addresses a critical gap by advocating for more stringent quality filtering, highlighting the imperative for a shift from existing standards, which currently lean towards greater permissiveness. We will show the importance of incorporating cell intronic fraction in quality control -or MALAT1 expression otherwise- showcasing its informative nature and potential to elevate cell atlas data reliability. In summary, here, we unveil the hidden intronic landscape of every tissue and highlight the importance of more rigorous single-cell RNA-sequencing quality assessment in cell atlases to enhance their applicability in diverse downstream analyses.

bioinformatics↗