Key Laboratory for Cell and Gene Engineering of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China.
Protein Cell. 2018 Mar;9(3):246-253. doi: 10.1007/s13238-017-0431-5. Epub 2017 Jun 8.
It was widely known that retinoic acid inducible gene I (RIG-I) functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent studies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations. While in hepatocellular carcinoma and acute myeloid leukemia, RIG-I acts as a tumor suppressor through either augmenting STAT1 activation by competitively binding STAT1 against its negative regulator SHP1 or inhibiting AKT-mTOR signaling pathway by directly interacting with Src respectively. These new findings suggest that RIG-I plays more diverse roles in various cellular life activities, such as cell proliferation and differentiation, than previously known. Taken together, the function of RIG-I exceeds far beyond that of a pattern recognition receptor.
众所周知，视黄酸诱导基因 I（RIG-I）作为一种细胞质模式识别受体，通过检测外源病毒 RNA 来启动先天抗病毒免疫。然而，最近的研究表明，RIG-I 通过在不同情况下感知内源性 RNA，参与其他各种细胞活动。例如，RIG-I 通过识别非编码 RNA 和内源性逆转录病毒，在某些情况下通过干扰素信号激活，促进乳腺癌细胞的治疗抵抗和扩增，并通过激活 T 细胞非依赖性 B 细胞激活。而在肝细胞癌和急性髓系白血病中，RIG-I 通过竞争性结合 STAT1 的负调节剂 SHP1 来增强 STAT1 的激活，或通过直接与Src 相互作用来抑制 AKT-mTOR 信号通路，分别作为肿瘤抑制因子发挥作用。这些新发现表明，RIG-I 在细胞增殖和分化等各种细胞生命活动中发挥的作用比以前已知的更为多样化。总之，RIG-I 的功能远远超出了模式识别受体的功能。
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