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Peer-reviewedCC BY 4.0Computational and Structural Biotechnology Journal

Genome-Wide Characterization of HERV-Derived RNA Regulatory Potential in the Human Transcriptome

  • Tomàs Montserrat-Ayuso1,2
  • Aurora Pujol3,4,5
  • Anna Esteve-Codina1,2
5 affiliations
  1. 1Centre Nacional d’Anàlisi Genòmica (CNAG), 08028 Barcelona, Spain .
  2. 2Universitat de Barcelona (UB), Barcelona, Spain .
  3. 3Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain .
  4. 4Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain .
  5. 5Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain .
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Abstract

Human endogenous retroviruses (HERVs) comprise nearly 8% of the human genome, and their long terminal repeats (LTRs) are well-established sources of transcriptional regulatory elements. However, their contribution to RNA-level regulatory features remains largely unexplored. Here, we present a genome-wide characterization of the RNA regulatory potential of 53,176 HERV internal regions and 560,594 LTRs. We found 16.2% more predicted RNA-binding protein motif occurrences in HERV internal regions than expected after controlling for dinucleotide composition. At the subfamily level, overall motif abundance was elevated in HERVH but remained close to expectation in HERVK (HML-2). Conserved retroviral protein domains incorporated into transcripts were mostly located in exceptionally long terminal exons, approximately 7-fold longer than those of other multi-exon transcripts. HERV internal sequence overlapped 4,074 annotated long noncoding RNA genes and accounted for more than 80% of the gene body of 144, most of them functionally unannotated. Finally, 6,583 unique antisense LTRs at transcript termini formed SPARCS-like candidate configurations that could support antisense RNA pairing; protein-coding genes carrying them in 3′ untranslated regions showed enrichment for immune signaling and recombination-related terms. These results provide a genome-wide framework of candidate HERV-derived RNA regulatory features and transcript architectures for experimental testing.

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Cite

BibTeXRIS
BibTeX
@article{montserratayuso2026genomewide,
  title = {{Genome-Wide Characterization of HERV-Derived RNA Regulatory Potential in the Human Transcriptome}},
  author = {Tomàs Montserrat-Ayuso and Aurora Pujol and Anna Esteve-Codina},
  journal = {Computational and Structural Biotechnology Journal},
  year = {2026},
  month = nov,
  doi = {10.34133/csbj.0244},
  url = {https://doi.org/10.34133/csbj.0244},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Genome-Wide Characterization of HERV-Derived RNA Regulatory Potential in the Human Transcriptome
AU  - Tomàs Montserrat-Ayuso
AU  - Aurora Pujol
AU  - Anna Esteve-Codina
PY  - 2026
DA  - 2026/11/05
JO  - Computational and Structural Biotechnology Journal
DO  - 10.34133/csbj.0244
UR  - https://doi.org/10.34133/csbj.0244
AB  - Human endogenous retroviruses (HERVs) comprise nearly 8% of the human genome, and their long terminal repeats (LTRs) are well-established sources of transcriptional regulatory elements. However, their contribution to RNA-level regulatory features remains largely unexplored. Here, we present a genome-wide characterization of the RNA regulatory potential of 53,176 HERV internal regions and 560,594 LTRs. We found 16.2% more predicted RNA-binding protein motif occurrences in HERV internal regions than expected after controlling for dinucleotide composition. At the subfamily level, overall motif abundance was elevated in HERVH but remained close to expectation in HERVK (HML-2). Conserved retroviral protein domains incorporated into transcripts were mostly located in exceptionally long terminal exons, approximately 7-fold longer than those of other multi-exon transcripts. HERV internal sequence overlapped 4,074 annotated long noncoding RNA genes and accounted for more than 80% of the gene body of 144, most of them functionally unannotated. Finally, 6,583 unique antisense LTRs at transcript termini formed SPARCS-like candidate configurations that could support antisense RNA pairing; protein-coding genes carrying them in 3′ untranslated regions showed enrichment for immune signaling and recombination-related terms. These results provide a genome-wide framework of candidate HERV-derived RNA regulatory features and transcript architectures for experimental testing.
SN  - 2001-0370
ER  -