Work

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

Year: 2026

Type: article

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.

Source: Computational and Structural Biotechnology Journal

DOI: 10.34133/csbj.0244

Authors: Tomàs Montserrat-Ayuso, Aurora Pujol, Anna Esteve-Codina