STING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2′3′-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production. The expression of STING-β declined in patients with lupus, in which type I IFNs are commonly overproduced. STING-β suppressed the induction of IFNs, IFN-stimulated genes and other cytokines by various immunostimulatory agents including cyclic dinucleotides, DNA, RNA and viruses, whereas depletion of STING-β showed the opposite effect. STING-β interacted with STING-α and antagonized its antiviral function. STING-β also interacted with TBK1 and prevented it from binding with STING-α, TRIF or other transducers. In addition, STING-β bound to 2′3′-cGAMP and impeded its binding with and activation of STING-α, leading to suppression of IFN-β production. Taken together, STING-β sequesters 2′3′-cGAMP second messenger and other transducer molecules to inhibit innate nucleic acid sensing dominantly.

中文翻译：

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隔离cGAMP并显着抑制先天核酸感测的STING的新型转录本亚型。

STING是哺乳动物细胞先天核酸传感中的核心衔接子，在其上不同的传感途径汇聚在一起，以诱导I型干扰素（IFN）的产生。特别是，STING被2'3'-cGAMP激活，2'3'-cGAMP是一种环状二核苷酸，含有混合的磷酸二酯键，由细胞质DNA传感器cGAS产生。在这里，我们报道了一种名为STING-β的STING的新型转录本亚型，该转录本主要抑制先天核酸的感应。没有跨膜结构域的STING-β在各种人体组织中以低水平广泛表达，并且STING-β的病毒诱导与IFN-β的产生呈负相关。狼疮患者中STING-β的表达下降，其中I型干扰素通常过量产生。STING-β抑制了IFN的诱导，各种免疫刺激剂（包括环二核苷酸，DNA，RNA和病毒）通过IFN刺激的基因和其他细胞因子，而STING-β的耗竭则显示相反的效果。STING-β与STING-α相互作用并拮抗其抗病毒功能。STING-β还与TBK1相互作用，并阻止它与STING-α，TRIF或其他传感器结合。此外，STING-β与2'3'-cGAMP结合并阻碍其与STING-α的结合和激活，从而导致IFN-β的产生受到抑制。两者合计，STING-β隔离2'3'-cGAMP第二信使和其他传感器分子，以抑制先天核酸显着抑制。STING-β还与TBK1相互作用，并阻止它与STING-α，TRIF或其他传感器结合。此外，STING-β与2'3'-cGAMP结合并阻碍其与STING-α的结合和激活，从而导致IFN-β的产生受到抑制。两者合计，STING-β隔离2'3'-cGAMP第二信使和其他传感器分子，以抑制先天核酸显着抑制。STING-β也与TBK1相互作用，并阻止它与STING-α，TRIF或其他传感器结合。另外，STING-β与2'3'-cGAMP结合并阻碍其与STING-α的结合和活化，从而导致IFN-β产生的抑制。两者合计，STING-β隔离2'3'-cGAMP第二信使和其他传感器分子，以抑制先天核酸显着抑制。