Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
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DOI：
10.1126/science.aad6780
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发表时间：
2016-01-22
期刊：
影响因子：
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通讯作者：
Rando OJ
中科院分区：
文献类型：
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作者：
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
最近的几项研究将亲本环境与后代的表型联系起来。在这里，我们调查的机制，父亲的饮食影响后代的新陈代谢。小鼠中的蛋白质限制影响成熟精子中的小RNA水平，使let-7水平降低，甘氨酸tRNA的5'片段水平增加。tRNA片段在睾丸精子中很少，但随着精子在附睾中成熟而获得。附睾体-在附睾运输过程中与精子融合的囊泡-携带与成熟精子相匹配的RNA有效载荷，并在体外将RNA传递给未成熟精子。在功能上，tRNA-Gly-GCC片段抑制与ES细胞和胚胎中的内源性逆转录元件MERVL相关的基因。我们的研究结果揭示了小RNA的生物合成，其饮食调节，在睾丸后精子成熟，并连接tRNA片段的调节内源性retroelements活跃在植入前胚胎。
Several recent studies link parental environments to phenotypes in subsequent generations. Here, we investigate the mechanism by which paternal diet affects offspring metabolism. Protein restriction in mice affects small RNA levels in mature sperm, with decreased let-7 levels and increased levels of 5’ fragments of glycine tRNAs. tRNA fragments are scarce in testicular sperm, but are gained as sperm mature in the epididymis. Epididymosomes – vesicles that fuse with sperm during epididymal transit – carry RNA payloads matching those of mature sperm, and deliver RNAs to immature sperm in vitro. Functionally, tRNA-Gly-GCC fragments repress genes associated with the endogenous retroelement MERVL, both in ES cells and embryos. Our results shed light on small RNA biogenesis, and its dietary regulation, during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the preimplantation embryo.