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PMID: 26721685 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Science (New York, N.Y.) ·Vol. 351 ·No. 6271 ·2016-01-22 ·Pages 391-396

Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, Belleannee C, Kucukural A, Serra RW, Sun F, Song L, Carone BR, Ricci EP, Li XZ, Fauquier L, Moore MJ, Sullivan R, Mello CC, Garber M, Rando OJ

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.

MeSH Terms
Animals Blastocyst/metabolism Diet, Protein-Restricted Epididymis/metabolism Fertilization Gene Expression Regulation Male Mice MicroRNAs/metabolism RNA, Transfer, Gly/metabolism,physiology Retroelements/genetics Sperm Maturation Spermatozoa/metabolism Testis/metabolism
Chemicals
MicroRNAs RNA, Transfer, Gly Retroelements mirnlet7 microRNA, mouse
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Sharma Upasna
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Conine Colin C
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Shea Jeremy M
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Boskovic Ana
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Derr Alan G
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.
Bing Xin Y
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Belleannee Clemence
Department of Obstetrics, Gynecology and Reproduction, Université Laval, Centre Hospitalier Universitaire de Québec Research Center,,Quebec City, Canada, G1V 4G2.
Kucukural Alper
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.
Serra Ryan W
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Sun Fengyun
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Song Lina
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Carone Benjamin R
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Ricci Emiliano P
RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Li Xin Z
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.
Fauquier Lucas
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Moore Melissa J
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.
Sullivan Robert
Department of Obstetrics, Gynecology and Reproduction, Université Laval, Centre Hospitalier Universitaire de Québec Research Center,,Quebec City, Canada, G1V 4G2.
Mello Craig C
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.
Garber Manuel
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.
Rando Oliver J
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.aad6780
Published
2016-01-22
Epub
2015-00-31
Pages
391-396
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4888079
Subset
IM
Grants
NICHD NIH HHS · R00 HD078482 · United States
NIEHS NIH HHS · DP1 ES025458 · United States
NCATS NIH HHS · UL1 TR001453 · United States
NCCDPHP CDC HHS · DP1ES025458 · United States
NICHD NIH HHS · R01 HD080224 · United States
NICHD NIH HHS · R01HD080224 · United States
NICHD NIH HHS · T32 HD007439 · United States
Howard Hughes Medical Institute · United States
Corrections
CommentIn
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External Links
PubMed source DOI: 10.1126/science.aad6780 PMC Full Text View journal details
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