Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals
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Abstract
Several recent studies link parental environments to phenotypes in subsequent generations. In this work, we investigate the mechanism by which paternal diet affects offspring metabolism. Protein restriction in mice affects small RNA (sRNA) levels in mature sperm, with decreased let-7 levels and increased amounts of 5' fragments of glycine transfer RNAs (tRNAs). In testicular sperm, tRNA fragments are scarce but increase in abundance as sperm mature in the epididymis. Epididymosomes (vesicles that fuse with sperm during epididymal transit) carry RNA payloads matching those of mature sperm and can deliver RNAs to immature sperm in vitro. Functionally, tRNA-glycine-GCC fragments repress genes associated with the endogenous retroelement MERVL, in both embryonic stem cells and embryos. Our results shed light on sRNA biogenesis and its dietary regulation during posttesticular sperm maturation, and they also link tRNA fragments to regulation of endogenous retroelements active in the preimplantation embryo.
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The record
- Venue
- Science
- Topic
- RNA modifications and cancer
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Centre hospitalier universitaire de Québec
- Funders
- National Center for Advancing Translational SciencesMarch of Dimes FoundationNational Institutes of HealthNational Institute of Environmental Health SciencesNational Center for Chronic Disease Prevention and Health PromotionEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentHoward Hughes Medical Institute
- Keywords
- BiologyOffspringSpermBiogenesisEpigeneticsPhenotypeTransfer RNAGeneticsHuman fertilizationMetabolic pathwayGeneEmbryoRNAAndrologyPregnancy
- Has abstract in OpenAlex
- yes