TLRs are blind to pseudouridine RNA

IF 27.6 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2025-07-29 DOI:10.1038/s41590-025-02251-2

Paula Jauregui

引用次数: 0

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tlr对假尿嘧啶RNA不可见

TLR7和TLR8对RNA的识别在病原体防御中起着重要作用。含有假尿嘧啶（Ψ）的RNA存在于内源性RNA中，因其缺乏免疫刺激活性而被用于mRNA疫苗。在Cell中，b routi等人确定了这种逃避toll样受体（TLR）识别的分子机制。通过质谱分析，作者发现RNase T2更倾向于RU基序，并且对Ψ RNA的活性降低。这避免了TLR8在原代人单核细胞和其他细胞类型中的激活。通过测量配体诱导二聚化的生化分析，作者得出结论，与u相比，Ψ是TLR8较弱的底物。在浆细胞样树突状细胞中，他们发现Ψ抑制RNase T2和PLD外切酶的有效降解，导致TLR7口袋1中2 ',3 ' -cGMP的释放受损，并且Ψ不能成为TLR7口袋2的配体。总之，作者表明溶酶体核酸酶不能充分地将Ψ-containing RNA加工成tlr -激动性配体，并且TLR8不能在其第一个结合袋中结合Ψ，而TLR7不能在其第二个结合袋中结合Ψ-containing片段。这种机制知识可以帮助合理设计基于rna的治疗方法。原始参考文献：Cell https://doi.org/10.1016/j.cell.2025.05.032 （2025）

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.