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

Upasna Sharma(University of Massachusetts Chan Medical School), Colin C. Conine(University of Massachusetts Chan Medical School), Jeremy M. Shea(University of Massachusetts Chan Medical School), Ana Bošković(University of Massachusetts Chan Medical School), Alan Derr(University of Massachusetts Chan Medical School), Xinyang Bing(University of Massachusetts Chan Medical School), Clémence Belleannée(Centre hospitalier universitaire de Québec), Alper Küçükural(University of Massachusetts Chan Medical School), Ryan W. Serra(University of Massachusetts Chan Medical School), Fengyun Sun(University of Massachusetts Chan Medical School), Lina Song(University of Massachusetts Chan Medical School), Benjamin R. Carone(University of Massachusetts Chan Medical School), Emiliano P. Ricci(University of Massachusetts Chan Medical School), Xin Z. Li(University of Massachusetts Chan Medical School), Lucas Fauquier(University of Massachusetts Chan Medical School), Melissa J. Moore(Howard Hughes Medical Institute), Robert Sullivan(Centre hospitalier universitaire de Québec), Craig C. Mello(Howard Hughes Medical Institute), Manuel Garber(University of Massachusetts Chan Medical School), Oliver J. Rando(University of Massachusetts Chan Medical School)
Science
December 31, 2015
10.1126/science.aad6780
Cited by 1,315Open Access
Full Text

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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