Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Primary Immunodeficiency Research Lab, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium.
Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, USA.
Trends Immunol. 2023 Jun;44(6):435-449. doi: 10.1016/j.it.2023.04.002. Epub 2023 May 4.
Nucleic acid sensors survey subcellular compartments for atypical or mislocalized RNA or DNA, ultimately triggering innate immune responses. Retinoic acid-inducible gene-I (RIG-I) is part of the family of cytoplasmic RNA receptors that can detect viruses. A growing literature demonstrates that mammalian RNA polymerase III (Pol III) transcribes certain viral or cellular DNA sequences into immunostimulatory RIG-I ligands, which elicits antiviral or inflammatory responses. Dysregulation of the Pol III-RIG-I sensing axis can lead to human diseases including severe viral infection outcomes, autoimmunity, and tumor progression. Here, we summarize the newly emerging role of viral and host-derived Pol III transcripts in immunity and also highlight recent advances in understanding how mammalian cells prevent unwanted immune activation by these RNAs to maintain homeostasis.
核酸传感器检测细胞区室中异常或定位错误的 RNA 或 DNA，最终触发先天免疫反应。视黄酸诱导基因-I (RIG-I) 是细胞质 RNA 受体家族的一部分，可识别病毒。越来越多的文献表明，哺乳动物 RNA 聚合酶 III (Pol III) 将某些病毒或细胞 DNA 序列转录成免疫刺激性的 RIG-I 配体，从而引发抗病毒或炎症反应。Pol III-RIG-I 感应轴的失调可导致人类疾病，包括严重的病毒感染结果、自身免疫和肿瘤进展。在这里，我们总结了病毒和宿主来源的 Pol III 转录物在免疫中的新作用，并强调了最近在理解哺乳动物细胞如何防止这些 RNA 引起不必要的免疫激活以维持体内平衡方面的进展。
