Inheritance of miRNAs via Yolk Promotes Stress Resilience in Progeny. Inheritance of miRNAs via Yolk Promotes Stress Resilience in Progeny

At the onset of reproduction, oviparous animals synthesize large amounts of yolk in somatic tissues to provide lipids and other nutrients to their progeny. However, whether the yolk transports other types of molecules, such as RNAs with gene regulatory functions, remains largely unexplored. Here, we have biochemically purified the yolk granules in the nematode Caenorhabditis elegans and show they contain microRNAs (miRNAs). We provide evidence that the yolk transports such miRNAs from the mother’s intestine to the embryos via the lipoprotein yolk receptor RME-2. These yolk-enriched miRNAs inherited by the embryos regulate the transcriptomes of developing larvae. Moreover, environmental stresses and maternal age modulate the transfer of yolk-enriched miRNAs, contributing to stress resilience benefits to progeny. This discovery establishes a novel paradigm in intergenerational gene regulation, where the gut-germline axis orchestrates the transmission of environmental cues through yolk-enriched miRNAs. Our work reveals a new mechanism underlying the soma-to-germline transfer of epigenetic information in animals. Overall design: RNA sequencing profiles of 2-cell embryos or freshly hatched L1 larvae.

在生殖起始阶段，卵生动物会在体细胞组织中合成大量卵黄，为后代提供脂质与其他营养物质。然而，卵黄是否能够转运其他类型的分子（例如具有基因调控功能的RNA），目前仍鲜有研究。本研究通过生化方法纯化了秀丽隐杆线虫（Caenorhabditis elegans）的卵黄颗粒，并证实其中含有微小RNA（microRNAs，miRNAs）。本研究进一步证实，卵黄可通过脂蛋白卵黄受体RME-2，将这类微小RNA从母体肠道转运至胚胎内。胚胎所继承的这类卵黄富集型微小RNA，可调控发育中幼虫的转录组。此外，环境压力与母体年龄可调控卵黄富集型微小RNA的转运，进而为后代带来应激抵抗益处。本发现为跨代基因调控建立了全新范式：肠道-生殖系轴通过卵黄富集型微小RNA，协调环境信号的传递。本研究揭示了动物体内表观遗传信息从体细胞向生殖系转运的全新机制。实验整体设计：2细胞胚胎或刚孵化的L1幼虫的RNA测序图谱。