308: PANDORA-seq reveals conserved rsRNA length shift and tsRNA/rsRNA aging cliff in mouse and human sperm

Shi J et al., The EMBO Journal, doi:10.1038/s44318-025-00687-8 - PANDORA-seq profiling of mouse and human sperm heads identifies a conserved rsRNA length shift with age and a tsRNA/rsRNA 'aging cliff' that reprograms embryonic transcripts. Key terms: sperm sncRNA, rsRNA length shift, PANDORA-seq, aging cliff, tRNA-derived small RNA.

Study Highlights:
Using PANDORA-seq on C57BL/6J mouse sperm (intact and de-membranated heads) across five age groups and two independent human sperm cohorts, the authors identify a sharp tsRNA/rsRNA "aging cliff" in mice between 50–70 weeks and a head-specific rsRNA length shift. PANDORA-seq overcomes modification-induced detection bias to reveal increases in longer rsRNAs and decreases in shorter rsRNAs, particularly from 28S- and 18S-rRNAs, with parallel trends in human cohorts. Mitochondrial tsRNAs/rsRNAs in sperm heads, although low abundance, covary with genomic sncRNAs and help distinguish age groups. Transfection of age-mimicking tsRNA/rsRNA cocktails into mouse embryonic stem cells reprograms gene expression, upregulating metabolic and neurodegeneration-related pathways, providing a functional link to offspring phenotypes.

Conclusion:
PANDORA-seq uncovers a conserved, sperm head–specific rsRNA length shift and a tsRNA/rsRNA aging cliff in mice and humans, and age-mimicking sncRNA combinations can alter embryonic transcriptomes linked to metabolic and neurodegenerative pathways.

Music:
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Article title:
Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging

First author:
Shi J

Journal:
The EMBO Journal, doi:10.1038/s44318-025-00687-8

DOI:
10.1038/s44318-025-00687-8

Reference:
Shi J, Zhang X, Cai C, Liu S, Yu J, James ER, et al. Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging. The EMBO Journal. 2026;45(4):1362–1380. https://doi.org/10.1038/s44318-025-00687-8

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-03-05.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantively audited the transcript segments describing (1) the aging cliff in mouse sperm tsRNA/rsRNA profiles, (2) rsRNA length shifts in sperm heads, (3) cross-species conservation in humans, (4) mitochondrial sncRNA patterns, (5) functional RNA transfection experiments in mouse embryonic stem cells, (6) the PANDOR
- transcript topics: PANDORA-seq methodology; mouse sperm aging cliff at 50-70 weeks; rsRNA length shift in mouse sperm heads (28S/18S origin); mitochondrial tsRNA/rsRNA patterns in sperm heads; conservation of rsRNA length shift in human sperm cohorts; functional reprogramming of mESC transcriptomes by age-mimicking sncRNA cocktails

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Aging cliff between 50 and 70 weeks in mouse sperm sncRNA profiles detected by PANDORA-seq.
- Sperm-head rsRNAs show an age-related length shift: longer rsRNAs increase and shorter rsRNAs decrease, especially from 28S- and 18S-derived rsRNAs.
- Conserved rsRNA length shift observed in humans across two independent cohorts (longitudinal and cross-sectional).
- Mitochondrial rsRNAs/tsRNAs detected in de-membranated sperm heads co-vary with genomic sncRNA aging patterns.
- Age-mimicking tsRNA/rsRNA cocktails transfected into mouse embryonic stem cells reprogram transcriptomes toward metabolic and neurodegeneration pathways.
- Pandora-seq overcomes RNA modification-induced detection bias to reveal previously undetectable sncRNA species.

QC result: Pass.