2016 January 22; 351(6271): 391–396 | Upasna Sharma#, Colin C. Conine#, Jeremy M. Shea, Ana Boskovic, Alan G. Derr, Xin Y. Bing, Clemence Belleannee, Alper Kucukural, Ryan W. Serra, Fengyun Sun, Lina Song, Benjamin R. Carone, Emiliano P. Ricci, Xin Z. Li, Lucas Fauquier, Melissa J. Moore, Robert Sullivan, Craig C. Mello, Manuel Garber, Oliver J. Rando
The study investigates how paternal diet affects offspring metabolism through changes in small RNA levels in mature sperm. Specifically, protein restriction in mice leads to decreased let-7 levels and increased levels of 5' fragments of glycine tRNAs (tRFs). These tRNA fragments are scarce in testicular sperm but increase during epididymal maturation. Epididymosomes, vesicles that fuse with sperm during epididymal transit, carry RNA payloads similar to those in mature sperm and deliver these RNAs to immature sperm in vitro. Functionally, tRF-Gly-GCC represses genes associated with the endogenous retroelement MERVL in both embryonic stem cells and embryos. The findings highlight the role of small RNA biogenesis and dietary regulation during post-testicular sperm maturation and suggest that epididymosomes play a crucial role in delivering tRFs to sperm.The study investigates how paternal diet affects offspring metabolism through changes in small RNA levels in mature sperm. Specifically, protein restriction in mice leads to decreased let-7 levels and increased levels of 5' fragments of glycine tRNAs (tRFs). These tRNA fragments are scarce in testicular sperm but increase during epididymal maturation. Epididymosomes, vesicles that fuse with sperm during epididymal transit, carry RNA payloads similar to those in mature sperm and deliver these RNAs to immature sperm in vitro. Functionally, tRF-Gly-GCC represses genes associated with the endogenous retroelement MERVL in both embryonic stem cells and embryos. The findings highlight the role of small RNA biogenesis and dietary regulation during post-testicular sperm maturation and suggest that epididymosomes play a crucial role in delivering tRFs to sperm.