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:Enjoy the music based on this article at the end of the episode. 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/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/sperm-rsrna-length-shift 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 sp...