Cross-species analysis identifies APOBEC3-associated spliceosomal snRNA hypermutability

Abstract

Spliceosomal small nuclear RNA (snRNA) genes show unusually high germline mutation rates, with R-loop formation previously implicated in this mutability. Our cross-species rare-variant and de novo mutation analyses show that hypermutability is concentrated in RNA polymerase II-transcribed spliceosomal snRNA genes, with strong enrichment in primates but a much weaker excess in rodents and chicken, consistent with lineage differences in APOBEC3 repertoires. Human Pol II-transcribed spliceosomal snRNA genes show mutational strand asymmetry, APOBEC3-associated mutational signatures and strong APOBEC3B binding signals. R-loops are also frequent at these loci, including in mouse genes with much weaker hypermutability, indicating that R-loop formation alone is insufficient to explain the phenotype. Together, cross-species comparisons support lineage-specific APOBEC3 activity, rather than R-loop formation alone, as a major contributor to spliceosomal snRNA gene hypermutability.

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BibTeX RIS

BibTeX

@misc{xue2026crossspecies,
  title = {{Cross-species analysis identifies APOBEC3-associated spliceosomal snRNA hypermutability}},
  author = {J. Xue and Z. Jiang and J. Zhang and C. Li},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.12.758683},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.12.758683v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Cross-species analysis identifies APOBEC3-associated spliceosomal snRNA hypermutability
AU  - J. Xue
AU  - Z. Jiang
AU  - J. Zhang
AU  - C. Li
PY  - 2026
DA  - 2026/10/12
PB  - bioRxiv
DO  - 10.64898/2026.10.12.758683
UR  - https://www.biorxiv.org/content/10.64898/2026.10.12.758683v1
AB  - Spliceosomal small nuclear RNA (snRNA) genes show unusually high germline mutation rates, with R-loop formation previously implicated in this mutability. Our cross-species rare-variant and de novo mutation analyses show that hypermutability is concentrated in RNA polymerase II-transcribed spliceosomal snRNA genes, with strong enrichment in primates but a much weaker excess in rodents and chicken, consistent with lineage differences in APOBEC3 repertoires. Human Pol II-transcribed spliceosomal snRNA genes show mutational strand asymmetry, APOBEC3-associated mutational signatures and strong APOBEC3B binding signals. R-loops are also frequent at these loci, including in mouse genes with much weaker hypermutability, indicating that R-loop formation alone is insufficient to explain the phenotype. Together, cross-species comparisons support lineage-specific APOBEC3 activity, rather than R-loop formation alone, as a major contributor to spliceosomal snRNA gene hypermutability.
ER  -

Abstract

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