ArticleThe Journal of biological chemistry2024
Epididymis-specific RNase A family genes regulate fertility and small RNA processing.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Breed-specific divergence in boar sperm regulatory profiles involves piRNA and mitochondrial small RNAs.Cellular and molecular life sciences : CMLS · 2026Article
- Paternal immune activation-induced alteration of 28S rRNA-derived small RNAs in sperm reprograms offspring phenotypes.PNAS nexus · 2026Article
- RNA Polymerase III-Transcribed RNAs in Health and Disease: Mechanisms, Dysfunction, and Future Directions.International journal of molecular sciences · 2025Review
- The functions and modifications of tRNA-derived small RNAs in cancer biology.Cancer metastasis reviews · 2025Review
- The Small Non-Coding RNA Profile of Human and Mouse Sperm.Non-coding RNA · 2025Review
- Ribonucleases of Mice and Men: Unveiling the Roles of the RNase A Superfamily in Host Defence.Journal of immunology research · 2025Review
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8 authors.
Funding
Abstract
Sperm small RNAs are implicated in intergenerational transmission of paternal environmental effects. Small RNAs generated by the cleavage of tRNAs, known as tRNA fragments (tRFs) or tRNA-derived RNAs (tDRs or tsRNAs), are an abundant class of RNAs in mature sperm and can be modulated by environmental conditions. The biogenesis of tRFs in the male reproductive tract remains poorly understood. Angiogenin, a member of the ribonuclease A superfamily (RNase A), cleaves tRNAs to generate tRFs in response to cellular stress. Four paralogs of Angiogenin, namely Rnase9, Rnase10, Rnase11, and Rnase12, are specifically expressed in the epididymis-a long, convoluted tubule where sperm mature and acquire fertility and motility. Here, by generating mice deleted for all four genes (Rnase9-12-/-, termed "KO" for Knock Out), we report that these genes regulate fertility and small RNA levels. KO male mice are sterile; KO sperm fertilized oocytes in vitro but failed to efficiently fertilize oocytes in vivo due to an inability of sperm to pass through the utero-tubular junction. Intriguingly, there were decreased levels of tRFs and rRNAs (rRNA-derived small RNAs or rsRNAs) in the KO epididymis and epididymal luminal fluid, although RNases 9-12 did not show ribonucleolytic activity in vitro. Importantly, KO sperm showed a dramatic decrease in the levels of tRFs, demonstrating a role of epididymis-specific Rnase9-12 genes in regulating sperm small RNA composition. Together, our results reveal an unexpected role of four epididymis-specific noncanonical ribonuclease A family genes in regulating fertility and small RNA processing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.