Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou 510632, P.R, China.
Theranostics. 2020 Jul 23;10(20):9407-9424. doi: 10.7150/thno.48520. eCollection 2020.
The diseases caused by viruses posed a great challenge to human health, the development of which was driven by the imbalanced host immune response. Host innate immunity is an evolutionary old defense system that is critical for the elimination of the virus. The overactive innate immune response also leads to inflammatory autoimmune diseases, which require precise control of innate antiviral response for maintaining immune homeostasis. Mounting long non-coding RNAs (lncRNAs) transcribed from the mammalian genome are key regulators of innate antiviral response, functions of which greatly depend on their protein interactors, including classical RNA-binding proteins (RBPs) and the unconventional proteins without classical RNA binding domains. In particular, several emerging RBPs, such as mA machinery components, TRIM family members, and even the DNA binding factors recognized traditionally, function in innate antiviral response. In this review, we highlight recent progress in the regulation of type I interferon signaling-based antiviral responses by lncRNAs and emerging RBPs as well as their mechanism of actions. We then posed the future perspective toward the role of lncRNA-RBP interaction networks in innate antiviral response and discussed the promising and challenges of lncRNA-based drug development as well as the technical bottleneck in studying lncRNA-protein interactions. Our review provides a comprehensive understanding of lncRNA and emerging RBPs in the innate antiviral immune response.
病毒引起的疾病对人类健康构成了巨大挑战，其发展是由宿主免疫反应失衡驱动的。宿主先天免疫是一种古老的防御系统，对于消除病毒至关重要。过度活跃的先天免疫反应也会导致炎症性自身免疫性疾病，这需要精确控制先天抗病毒反应以维持免疫平衡。哺乳动物基因组转录的长非编码 RNA（lncRNA）是先天抗病毒反应的关键调节剂，其功能在很大程度上取决于其蛋白质相互作用物，包括经典 RNA 结合蛋白（RBPs）和没有经典 RNA 结合结构域的非常规蛋白。特别是，一些新兴的 RBPs，如 mA 机器组件、TRIM 家族成员，甚至是传统上被认为是 DNA 结合因子的蛋白，都在先天抗病毒反应中发挥作用。在这篇综述中，我们强调了 lncRNA 和新兴 RBPs 对 I 型干扰素信号转导为基础的抗病毒反应的调控作用及其作用机制。然后，我们提出了关于 lncRNA-RBP 相互作用网络在先天抗病毒反应中的作用的未来展望，并讨论了基于 lncRNA 的药物开发的前景和挑战以及研究 lncRNA-蛋白相互作用的技术瓶颈。我们的综述提供了对 lncRNA 和新兴 RBPs 在先天抗病毒免疫反应中的全面理解。
