title: Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Upasna
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Conine
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Shea
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Boskovic
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.|Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Derr
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Xin Y
authors.initials: XY
authors.lastname: Bing
authors.affiliation: Department of Obstetrics, Gynecology and Reproduction, Université Laval, Centre Hospitalier Universitaire de Québec Research Center,,Quebec City, Canada, G1V 4G2.
authors.forename: Clemence
authors.initials: C
authors.lastname: Belleannee
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.|Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Alper
authors.initials: A
authors.lastname: Kucukural
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Serra
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Carone
authors.affiliation: RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Emiliano P
authors.initials: EP
authors.lastname: Ricci
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.|RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Xin Z
authors.initials: XZ
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Fauquier
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.|RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.|Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Moore
authors.affiliation: Department of Obstetrics, Gynecology and Reproduction, Université Laval, Centre Hospitalier Universitaire de Québec Research Center,,Quebec City, Canada, G1V 4G2.
authors.forename: Robert
authors.initials: R
authors.lastname: Sullivan
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.|RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.|Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.|Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Garber
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D018753:Diet, Protein-Restricted; D004822:Epididymis / Q000378:metabolism; D005306:Fertilization; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D012353:RNA, Transfer, Gly / Q000378:metabolism* / Q000502:physiology*; D018626:Retroelements / Q000235:genetics; D013079:Sperm Maturation; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012353:RNA, Transfer, Gly; D018626:Retroelements; C542687:mirnlet7 microRNA, mouse