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

Upasna Sharma (1) , C. Conine , Jeremy M Shea , Ana A. Boskovic (2) , Alan G Derr , Xin y Bing , Clémence Belleannée (3) , Alper Kucukural , R. Serra (4) , Fengyun Sun , Lina Song (5) , Benjamin R Carone , Emiliano P Ricci (6) , Xin Z Li , Lucas Fauquier , Melissa J Moore , Robert Sullivan , Craig C Mello , Manuel Garber (7) , Oliver J Rando

1 CNRC - Conseil National de Recherches Canada
2 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
3 Faculté de Médecine
4 Istituto Nazionale di Fisica della Materia
5 Key Laboratory of Ocean Circulation and Waves, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
6 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
7 Broad Institute [Cambridge]

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 †

Domaines: Biochimie, Biologie Moléculaire; Biologie cellulaire

Upasna Sharma, C. Conine, Jeremy M Shea, Ana A. Boskovic, Alan G Derr, et al.. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science, 2016, 351 (6271), pp.391-396. ⟨10.1126/science.aad6780⟩. ⟨hal-02444484⟩