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新型环状 RNA 通过海绵吸附 miRNA 来介导模块丝氨酸蛋白酶的积累,从而增强埃及伊蚊对真菌的免疫力。

The accumulation of modular serine protease mediated by a novel circRNA sponging miRNA increases Aedes aegypti immunity to fungus.

机构信息

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

BMC Biol. 2024 Jan 17;22(1):7. doi: 10.1186/s12915-024-01811-6.

Abstract

BACKGROUND

Mosquitoes transmit many infectious diseases that affect human health. The fungus Beauveria bassiana is a biological pesticide that is pathogenic to mosquitoes but harmless to the environment.

RESULTS

We found a microRNA (miRNA) that can modulate the antifungal immunity of Aedes aegypti by inhibiting its cognate serine protease. Fungal infection can induce the expression of modular serine protease (ModSP), and ModSP knockdown mosquitoes were more sensitive to B. bassiana infection. The novel miRNA-novel-53 is linked to antifungal immune response and was greatly diminished in infected mosquitoes. The miRNA-novel-53 could bind to the coding sequences of ModSP and impede its expression. Double fluorescence in situ hybridization (FISH) showed that this inhibition occurred in the cytoplasm. The amount of miRNA-novel-53 increased after miRNA agomir injection. This resulted in a significant decrease in ModSP transcript and a significant increase in mortality after fungal infection. An opposite effect was produced after antagomir injection. The miRNA-novel-53 was also knocked out using CRISPR-Cas9, which increased mosquito resistance to the fungus B. bassiana. Moreover, mosquito novel-circ-930 can affect ModSP mRNA by interacting with miRNA-novel-53 during transfection with siRNA or overexpression plasmid.

CONCLUSIONS

Novel-circ-930 affects the expression level of ModSP by a novel-circ-930/miRNA-novel-53/ModSP mechanism to modulate antifungal immunity, revealing new information on innate immunity in insects.

摘要

背景

蚊子传播多种传染病,影响人类健康。真菌球孢白僵菌是一种对蚊子具有致病性但对环境无害的生物农药。

结果

我们发现了一种 microRNA(miRNA),它可以通过抑制其同源丝氨酸蛋白酶来调节埃及伊蚊的抗真菌免疫。真菌感染可以诱导模块化丝氨酸蛋白酶(ModSP)的表达,而 ModSP 敲低的蚊子对 B. bassiana 的感染更为敏感。新型 miRNA-novel-53 与抗真菌免疫反应有关,在感染的蚊子中大大减少。miRNA-novel-53 可以与 ModSP 的编码序列结合并阻碍其表达。双荧光原位杂交(FISH)显示这种抑制发生在细胞质中。miRNA agomir 注射后 miRNA-novel-53 的含量增加。这导致 ModSP 转录物显著减少,真菌感染后的死亡率显著增加。反义寡核苷酸(antagomir)注射后则产生相反的效果。使用 CRISPR-Cas9 敲除 miRNA-novel-53 也会增加蚊子对真菌 B. bassiana 的抗性。此外,在转染 siRNA 或过表达质粒时,蚊子 novel-circ-930 可以通过与 miRNA-novel-53 相互作用来影响 ModSP mRNA。

结论

novel-circ-930 通过 novel-circ-930/miRNA-novel-53/ModSP 机制影响 ModSP 的表达水平,从而调节抗真菌免疫,为昆虫先天免疫提供了新信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c26/10795361/98b4017a68fc/12915_2024_1811_Fig1_HTML.jpg

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