Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.

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.

Abstract:

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.