# Genetic polymorphisms lead to major, locus-specific, variation in piRNA production in mouse

**Authors:** Eduard Casas, Adrià Mitjavila-Ventura, Pío Sierra, Cristina Moreta-Moraleda, Judith Cebria, Ilaria Panzeri, J Andrew Pospisilik, Josep C Jimenez-Chillaron, Sonia V Forcales, Tanya Vavouri

PMC · DOI: 10.1038/s44318-025-00475-4 · The EMBO Journal · 2025-06-05

## TL;DR

This study shows that genetic differences between mouse strains lead to major variation in piRNA production, especially at loci with retrovirus insertions.

## Contribution

The study identifies genetic polymorphisms and retrovirus insertions as key drivers of strain-specific piRNA expression in mice.

## Key findings

- Genetic variation is a major determinant of piRNA expression differences between mouse strains.
- Endogenous retrovirus insertions are associated with polymorphic expression of piRNAs.
- An IAP retrovirus insertion in the gene Noct is linked to piRNA production in specific mouse strains.

## Abstract

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that silence transposons in the animal germline. PiRNAs are produced from long single-stranded noncoding transcripts, from protein-coding transcripts, as well as from transposons. While some sites that produce piRNAs are in deeply conserved syntenic regions, in general, piRNAs and piRNA-producing loci turnover faster than other functional parts of the genome. To learn about the sequence changes that contribute to the fast evolution of piRNAs, we set out to analyze piRNA expression between genetically different mice. Here we report the sequencing and analysis of small RNAs from the mouse male germline of four classical inbred strains, one inbred wild-derived strain and one outbred strain. We find that genetic differences between individuals underlie variation in piRNA expression. We report significant differences in piRNA production at loci with endogenous retrovirus insertions. Strain-specific piRNA-producing loci include protein-coding genes. Our findings provide evidence that transposable elements contribute to inter-individual differences in expression, and potentially to the fast evolution of piRNA-producing loci in mammals.

PIWI-interacting RNAs (piRNAs) are fast-evolving small RNAs expressed in the germline. This study reveals variation in locus-specific piRNA production between mouse strains, associated with endogenous retrovirus insertions.

Different mouse strains express piRNAs at different levels and some piRNAs are strain-specific.Genetic variation is a major determinant of piRNA expression differences between individuals.Endogenous retrovirus insertions are associated with polymorphic expression of piRNAs.The insertion of an IAP endogenous retrovirus in the intron of protein-coding gene Noct, is associated with piRNA production from the locus in mouse strains that carry the insertion.

Different mouse strains express piRNAs at different levels and some piRNAs are strain-specific.

Genetic variation is a major determinant of piRNA expression differences between individuals.

Endogenous retrovirus insertions are associated with polymorphic expression of piRNAs.

The insertion of an IAP endogenous retrovirus in the intron of protein-coding gene Noct, is associated with piRNA production from the locus in mouse strains that carry the insertion.

Small RNA sequencing from genetically divergent mouse strains shows that genetic differences are a major determinant for piRNA expression diversity.

## Linked entities

- **Genes:** NOCT (nocturnin) [NCBI Gene 25819]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12264111/full.md

## References

7 references — full list in the complete paper: https://tomesphere.com/paper/PMC12264111/full.md

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Source: https://tomesphere.com/paper/PMC12264111