SID-2 negatively regulates development likely independent of nutritional dsRNA uptake.

SID-2 negatively regulates development likely independent of nutritional dsRNA uptake.
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SID-2负调节发育可能独立于营养dsRNA摄取。

DOI:
10.1080/15476286.2020.1827619
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发表时间:
2021-06
期刊:
影响因子:
4.1
通讯作者:
Miska EA
Miska EA
中科院分区:
生物学3区
文献类型:
--
作者:
Braukmann F;Jordan D;Jenkins B;Koulman A;Miska EA

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RNA干扰(RNA interference, RNAi)是一种基于RNA-RNA相互作用的基因调控机制,在真核生物中保守存在。令人惊讶的是,许多动物可以从环境中摄取人类制造的双链RNA (dsRNA)来启动RNAi,这表明生物与其环境之间存在一种基于dsRNA的信息交换机制。然而,自22年前发现这一现象以来,还没有发现任何自然发生的例子。因此,为什么动物能够接受dsRNA仍然是个谜。在这里,我们通过对秀丽隐杆线虫的dsRNA摄取缺陷sid2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在使用基因致敏突变体的喂养实验中没有营养作用。此外,我们使用机器人辅助成像来显示sid-2突变体在孵化时加速了生长速度,并且通过母体的贡献,增加了体长。最后,我们进行了转录组和脂质组分析,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。总的来说,这些结果表明,sid-2对发育有轻微影响,不太可能在dsRNA的营养摄取中起作用。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。
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.
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