Sharma U1, Conine CC1, Shea JM1, Boskovic A1, Derr AG2, Bing XY1, Belleannee C3, Kucukural A2, Serra RW1, Sun F1, Song L1, Carone BR1, Ricci EP4, Li XZ5, Fauquier L1, Moore MJ6, Sullivan R3, Mello CC7,Garber M2, Rando OJ8.
Several recent studies link parental environments to phenotypes in subsequent generations. Here, we investigate the mechanism by which paternal diet affects offspring metabolism. Protein restriction in mice affects small RNA levels in mature sperm, with decreased let-7 levels and increased levels of 5′ fragments of glycine tRNAs. tRNA fragments are scarce in testicular sperm, but are gained as sperm mature in the epididymis. Epididymosomes-vesicles that fuse with sperm during epididymal transit-carry RNA payloads matching those of mature sperm, and deliver RNAs to immature sperm in vitro. Functionally, tRNA-Gly-GCC fragments repress genes associated with the endogenous retroelement MERVL, both in ES cells and embryos. Our results shed light on small RNA biogenesis and its dietary regulation during post-testicular sperm maturation and link tRNA fragments to regulation of endogenous retroelements active in the preimplantation embryo.