ABSTRACT

RNA interference (RNAi) is a gene regulatory mechanism based on RNA-RNA interaction conserved through eukaryotes. Surprisingly, many animals can take-up human-made double stranded RNA (dsRNA) from the environment to initiate RNAi suggesting a mechanism for dsRNA-based information exchange between organisms and their environment. However, no naturally occurring example has been identified since the discovery of the phenomenon 22 years ago. Therefore it remains enigmatic why animals are able to take up dsRNA. Here, we explore other possible functions by performing phenotypic studies of dsRNA uptake deficient sid-2 mutants in Caenorhabditis elegans. We find that SID-2 does not have a nutritional role in feeding experiments using genetic sensitized mutants. Furthermore, we use robot assisted imaging to show that sid-2 mutants accelerate growth rate and, by maternal contribution, body length at hatching. Finally, we perform transcriptome and lipidome analysis showing that sid-2 has no effect on energy storage lipids, but affects signalling lipids and the embryo transcriptome. Overall, these results suggest that sid-2 has mild effects on development and is unlikely functioning in the nutritional uptake of dsRNA. These findings broaden our understanding of the biological role of SID-2 and motivate studies identifying the role of environmental dsRNA uptake.

 抽象的

RNA 干扰 (RNAi) 是一种基于真核生物中保守的 RNA-RNA 相互作用的基因调控机制。令人惊讶的是，许多动物可以从环境中摄取人造双链 RNA (dsRNA) 来启动 RNAi，这表明生物体与其环境之间存在基于 dsRNA 的信息交换机制。然而，自 22 年前发现这种现象以来，尚未发现任何自然发生的例子。因此，动物为何能够摄取 dsRNA 仍然是个谜。在这里，我们通过对秀丽隐杆线虫中 dsRNA 摄取缺陷的sid-2突变体进行表型研究来探索其他可能的功能。我们发现 SID-2 在使用遗传致敏突变体的喂养实验中不具有营养作用。此外，我们使用机器人辅助成像表明sid-2突变体加速了生长速度，并且通过母体的贡献，加速了孵化时的体长。最后，我们进行转录组和脂质组分析，结果表明sid-2对能量储存脂质没有影响，但影响信号脂质和胚胎转录组。总体而言，这些结果表明sid-2对发育有轻微影响，并且不太可能在 dsRNA 的营养摄取中发挥作用。这些发现拓宽了我们对 SID-2 生物学作用的理解，并激发了确定环境 dsRNA 摄取作用的研究。