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Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder

Science  31 Dec 2015:

DOI: 10.1126/science.aad7977

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Abstract

Increasing evidence indicates that offspring metabolic disorders can result from the father’s diet, but the mechanism remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we show that a subset of sperm tRNA-derived small RNAs (tsRNAs), mainly from 5′ tRNA halves and ranging in size from 30 to 34 nucleotides, exhibit changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD male into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a type of paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorder.

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