RNA结合蛋白与巨噬细胞炎症因子表达

RNA-binding Proteins and Expression of Inflammatory Factors in Macrophages

RNA结合蛋白(RNA-binding proteins, RBPs)是转录后基因表达的关键调控因子,参与剪接、出核、翻译和稳定性等RNA代谢调控。RBPs表达或功能异常可导致炎症性疾病、代谢性疾病以及神经系统疾病等多种疾病的发生发展。炎症是机体对外界刺激及损伤的防御性免疫反应。巨噬细胞作为机体重要的免疫细胞,通过快速响应刺激并且释放大量炎症因子,进而调控炎症反应。巨噬细胞中炎症因子的表达受到转录以及转录后水平的调控。其中,RBPs参与大量RNA的转录后调控过程。研究发现,一方面,RBPs直接结合炎症因子mRNA中的顺式作用元件,参与其mRNA稳定性和翻译等过程,例如TTP(tristetraprolin);另一方面,某些RBPs通过参与炎症信号通路中一些关键基因mRNA的稳定性、翻译或选择性剪接调控,进而间接影响炎症因子表达及分泌。例如,剪接因子3A亚基1(splicing factor 3A subunit 1, SF3A1)。本文主要总结RBPs在mRNA稳定性、翻译和选择性剪接不同转录后水平调控巨噬细胞炎症因子表达的作用机制。这些RBPs从不同的层面直接或者间接参与调控炎症因子的表达,有些相互协同,有些相互拮抗,是宏观的、整体的对机体炎症反应的调控。深入探讨RBPs调控巨噬细胞炎症因子以及炎症反应的作用机制,对于从不同角度认识、预防以及治疗炎症性相关疾病,具有重要意义。

RNA-binding proteins(RBPs) are essential regulators of gene expression in post-transcriptional levels, involving in regulating all aspects of RNA metabolism, including splicing, nuclear export, translation, and stability. Abnormal expression or dysfunction of RBPs could lead to a variety of diseases including inflammatory diseases, metabolic diseases, neurological disorders, and other diseases. Inflammation is the body’s defensive immune response to external stimuli and injuries. Macrophages, as important immune cells in the body, regulate inflammatory response by rapidly responding to stimuli and releasing a large number of inflammatory factors. The expression of inflammatory factors in macrophages is regulated at transcriptional and post-transcriptional levels, in which various RBPs participate in the post-transcriptional regulation. It is reported that, on the one hand, RBPs directly bind to the cis-acting element of inflammatory genes in order to regulate mRNA stability, or translation processes, such as TTP(tristetraprolin). On the other hand, some RBPs indirectly affect the expression and secretion of inflammatory factors, such as SF3 A1(splicing factor 3 A subunit 1), by participating in the regulation of mRNA of some key genes in the inflammatory signaling pathway at the post-transcriptional levels. In this review, we focus on the mechanisms by which RBPs regulate the expression of inflammatory cytokines in macrophages at different post-transcriptional levels of mRNA stability, translation, and alternative splicing. These RBPs are directly or indirectly involved in the expression of inflammatory factors by different ways, such as cooperating with each other or antagonizing each other. It is of great significance to explore the regulatory mechanism of RBPs in inflammatory factors and inflammatory responses of macrophages, for understanding, prevention, and treatment of inflammatory diseases from different perspectives.