STING Nuclear Partners Contribute to Innate Immune Signalling Responses
STING Nuclear Partners Contribute to Innate Immune Signalling Responses
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DOI：
10.1101/2020.12.21.423744
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Charles R. Dixon;P. Malik;J. I. de las Heras;Natalia Saiz-Ros;Flávia de Lima Alves;Mark Tingey;E. Gaunt;A. C. Richardson;David A. Kelly;Martin W. Goldberg;Greg J Towers;Weidong Yang;J. Rappsilber;P. Digard;E. C. Schirmer
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作者：
Charles R. Dixon;P. Malik;J. I. de las Heras;Natalia Saiz-Ros;Flávia de Lima Alves;Mark Tingey;E. Gaunt;A. C. Richardson;David A. Kelly;Martin W. Goldberg;Greg J Towers;Weidong Yang;J. Rappsilber;P. Digard;E. C. Schirmer
STING和cGAS通过识别细胞质病原体dsDNA并激活来自ER的信号传导级联来启动先天性免疫应答（IIR）;然而，另一个较少研究的STING库存在于核膜中。我们发现，STING在内核膜增加流动性和改变定位后，IIR激活双链DNA和poly（I：C）刺激。接下来，我们从孤立的核膜中识别了STING的核伙伴。这些包括几种已知的核膜蛋白，布罗莫结构域和表观遗传酶，以及RNA或DNA结合蛋白。引人注目的是，已知这些DNA和RNA结合STING配偶体中有17种与IRF 3/7转录因子的直接配偶体结合，IRF 3/7转录因子是IIR的中心驱动因子。我们发现这些STING伴侣中的几个-SYNCRIP，Men 1，Ddx 5，snRNP 70，RPS 27 a，Aatf-可以有助于IIR激活，并且SYNCRIP还可以保护免受甲型流感病毒感染。这些数据表明，STING的许多作用可能反映了它与多种RNA和DNA结合蛋白的相互作用，这些蛋白也在IIR中发挥作用。
STING and cGAS initiate innate immune responses (IIR) by recognizing cytoplasmic pathogen dsDNA and activating signaling cascades from the ER; however, another less investigated pool of STING resides in the nuclear envelope. We find that STING in the inner nuclear membrane increases mobility and changes localization upon IIR activation both from dsDNA and poly(I:C) stimuli. We next identified nuclear partners of STING from isolated nuclear envelopes. These include several known nuclear membrane proteins, bromodomain and epigenetic enzymes, and RNA- or DNA-binding proteins. Strikingly, 17 of these DNA and RNA-binding STING partners are known to bind direct partners of the IRF3/7 transcription factors that are central drivers of IIR. We find that several of these STING partners —SYNCRIP, Men1, Ddx5, snRNP70, RPS27a, Aatf— can contribute to IIR activation and SYNCRIP can moreover protect against influenza A virus infection. These data suggest that the many roles identified for STING likely reflect its interactions with multiple RNA and DNA-binding proteins that also function in IIR.