Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
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精子 tsRNA 有助于获得性代谢紊乱的代际遗传
DOI：
10.1126/science.aad7977
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发表时间：
2016-01-22
期刊：
影响因子：
56.9
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
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作者：
Chen, Qi;Yan, Menghong;Zhou, Qi
精子小RNA对后代的影响哺乳动物中父亲的饮食条件影响后代的代谢表型。虽然先前的工作表明表观遗传途径的参与，其机制仍不清楚。两项研究表明，改变父亲的饮食会影响小鼠精子中小RNA的水平。Chen等人将高脂饮食的雄性精子的精子转移RNA（tRNA）片段注射到正常的卵母细胞中。后代表现出代谢紊乱和伴随的代谢途径基因的改变。Sharma等人观察了小tRNA衍生片段在精子成熟过程中的生物发生和功能。进一步了解子代受亲代暴露影响的机制可能会影响人类疾病，如饮食诱导的代谢紊乱。《科学》，本期第397页，第391页精子中的转移RNA片段作为父亲的表观遗传因素与饮食诱导的后代代谢问题有关。越来越多的证据表明，父亲的饮食可能会导致后代的代谢紊乱，但其机制仍不清楚。在给予高脂饮食（HFD）的雄性小鼠模型中，我们发现精子转移RNA衍生的小RNA（tsRNA）的一个子集，主要来自5′转移RNA的一半，大小从30到34个核苷酸，表现出表达谱和RNA修饰的变化。将来自HFD雄性的精子tsRNA组分注射到正常受精卵中，在F1后代中产生代谢紊乱，并改变了F1后代早期胚胎和胰岛中代谢途径的基因表达，这与CpG富集区域的DNA甲基化无关。因此，精子tsRNA代表了一种父系表观遗传因子，可能介导饮食诱导的代谢紊乱的代际遗传。
Offspring affected by sperm small RNAs Paternal dietary conditions in mammals influence the metabolic phenotypes of offspring. Although prior work suggests the involvement of epigenetic pathways, the mechanisms remains unclear. Two studies now show that altered paternal diet affects the level of small RNAs in mouse sperm. Chen et al. injected sperm transfer RNA (tRNA) fragments from males that had been kept on a high-fat diet into normal oocytes. The progeny displayed metabolic disorders and concomitant alteration of genes in metabolic pathways. Sharma et al. observed the biogenesis and function of small tRNA-derived fragments during sperm maturation. Further understanding of the mechanisms by which progeny are affected by parental exposure may affect human diseases such as diet-induced metabolic disorders. Science, this issue p. 397, p. 391 Fragments of transfer RNA in sperm serve as paternal epigenetic factors linked to diet-induced metabolic problems in their offspring. Increasing evidence indicates that metabolic disorders in offspring can result from the father’s diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA–derived small RNAs (tsRNAs), mainly from 5′ transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males 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 paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.