The SKIV2L RNA exosome limits activation of the RIG-I-like receptors.
The SKIV2L RNA exosome limits activation of the RIG-I-like receptors.
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必须调节细胞内核酸的先天免疫传感器，以防止内源性DNA和RNA的不适当激活。外切酶Trex1通过代谢触发它的潜在DNA配体来调节DNA传感途径。然而，调控检测RNA的rig - i样受体（RLRs）的类似机制尚不清楚。我们发现SKIV2L RNA外泌体有效地限制了rlr的激活。我们发现，未折叠蛋白反应（UPR）通过ires -1核酸内切酶切割细胞rna产生内源性RLR配体，在skiv2l缺失的细胞中触发I型干扰素（IFN）的产生。SKIV2L缺乏症患者外周血中有I型IFN信号。我们的研究结果揭示了免疫刺激RNA的细胞内代谢机制，具有特异性自身免疫性疾病的意义。
Innate immune sensors of intracellular nucleic acids must be regulated to prevent inappropriate activation by endogenous DNA and RNA. The exonuclease Trex1 regulates the DNA sensing pathway by metabolizing potential DNA ligands that trigger it. However, an analogous mechanism for regulating the RIG-I-like receptors (RLRs) that detect RNA remains unknown. We show that the SKIV2L RNA exosome potently limits the activation of RLRs. We find that the unfolded protein response (UPR), which generates endogenous RLR ligands through IRE-1 endonuclease cleavage of cellular RNAs, triggers type I interferon (IFN) production in SKIV2L-depleted cells. Humans with SKIV2L deficiency have a type I IFN signature in their peripheral blood. Our findings reveal a mechanism for intracellular metabolism of immunostimulatory RNA, with implications for specific autoimmune disorders.
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