Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan.
Laboratory of Regulatory Information, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8397, Japan.
Sci Rep. 2023 Apr 18;13(1):6318. doi: 10.1038/s41598-023-33208-w.
Retinoic acid-inducible gene I (RIG-I) is the most front-line cytoplasmic viral RNA sensor and induces antiviral immune responses. RIG-I recognizes short double-stranded (dsRNA) (< 500 bp), but not long dsRNA (> 500 bp) to trigger antiviral signaling. Since RIG-I is capable of binding with dsRNA irrespective of size, length-dependent RIG-I signaling remains elusive. Here, we demonstrated that RIG-I bound to long dsRNA with slow kinetics. Remarkably, RIG-I/short dsRNA complex efficiently dissociated in an ATP hydrolysis-dependent manner, whereas RIG-I/long dsRNA was stable and did not dissociate. Our study suggests that the dissociation of RIG-I from RIG-I/dsRNA complex could be a step for efficient antiviral signaling. Dissociated RIG-I exhibited homo-oligomerization, acquiring ability to physically associate with MAVS, and biological activity upon introduction into living cells. We herein discuss common and unique mechanisms of viral dsRNA recognition by RIG-I and MDA5.
视黄酸诱导基因 I（RIG-I）是最前线的细胞质病毒 RNA 传感器，可诱导抗病毒免疫反应。RIG-I 识别短双链 RNA（<500bp），但不识别长双链 RNA（>500bp）以触发抗病毒信号。由于 RIG-I 能够结合无论大小的 dsRNA，因此长度依赖性的 RIG-I 信号仍然难以捉摸。在这里，我们证明 RIG-I 以缓慢的动力学与长 dsRNA 结合。值得注意的是，RIG-I/短 dsRNA 复合物以 ATP 水解依赖性的方式有效解离，而 RIG-I/长 dsRNA 则稳定且不会解离。我们的研究表明，RIG-I 从 RIG-I/dsRNA 复合物中的解离可能是有效抗病毒信号的一个步骤。解离的 RIG-I 表现出同源寡聚化，获得与 MAVS 物理结合的能力，并在引入活细胞后具有生物活性。我们在此讨论 RIG-I 和 MDA5 识别病毒 dsRNA 的共同和独特机制。
