RNA caps are deposited at the 5′ end of RNA polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5′-triphosphate RNAs are generated by RNA polymerase III transcription, including tRNAs, Alu RNAs, or vault RNAs. These RNAs have emerged as key players of innate immunity, as they can be recognized by the antiviral sensors. Mechanisms that regulate the presence of 5′-triphosphates, such as 5′-end dephosphorylation or RNA editing, prevent immune recognition of endogenous RNAs and excessive inflammation. Here, we provide a comprehensive overview of the complexity of RNA cap structures and 5′-triphosphate RNAs, highlighting their roles in transcript identity, immune surveillance, and disease.

中文翻译：

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RNA 5′端的分子语言：RNA身份和免疫的守护者

RNA 帽沉积在 RNA 聚合酶 II 转录本的 5' 端。除了将转录物标记为自身之外，这种修饰还调节基因表达的几个步骤，以使先天免疫系统能够将它们与无帽外源 RNA（包括源自病毒的 RNA）区分开来。专门的免疫传感器，例如 RIG-I 和 IFIT，在识别无帽细胞质转录物后触发抗病毒反应。有趣的是，哺乳动物宿主也可以产生无帽转录本。例如，5'-三磷酸RNA是由RNA聚合酶III转录产生的，包括tRNA、Alu RNA或vault RNA。这些 RNA 已成为先天免疫的关键参与者，因为它们可以被抗病毒传感器识别。调节 5'-三磷酸存在的机制，例如 5' 末端去磷酸化或 RNA 编辑，可防止内源性 RNA 的免疫识别和过度炎症。在这里，我们全面概述了 RNA 帽结构和 5'-三磷酸 RNA 的复杂性，强调了它们在转录本身份、免疫监视和疾病中的作用。