可变剪接在自身免疫性疾病中的研究进展  

Research progress of alternative splicing in autoimmune diseases

作　　者：储依然 徐胜前[1] CHU Yiran;XU Shengqian(Department of Rheumatology,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China)

机构地区：[1]安徽医科大学第一附属医院风湿免疫科,安徽合肥230022

出　　处：《中华全科医学》2023年第7期1211-1214,1228,共5页Chinese Journal of General Practice

基　　金：吴阶平医学基金会临床科研专项资助基金项目(320.6750.2020-03-4)。

摘　　要：可变剪接(alternative splicing,AS)是一种调节基因表达的一般机制,高达95%的人类基因经历了AS,这意味着这种转录后调节机制对几乎所有细胞过程都至关重要。AS的总体功能是增加从基因组表达的mRNA的多样性。AS会改变mRNA编码的蛋白质,从而产生深远的功能影响。在后生动物免疫系统的基因产物中也观察到AS,这些免疫系统已进化到能够有效识别病原体并区分“自我”和“非自我”,这可能得益于AS提供了其多样性和灵活性。人体免疫反应是一个复杂的过程,它响应许多外源性抗原,防止微生物感染,以及监测肿瘤和自身免疫性疾病的内源性成分,并且需要大量分子来支撑功能复杂的免疫活动。前mRNA的可变剪接通过产生多种转录亚型以补充与免疫反应相关的有限基因的功能,在免疫细胞发育和免疫活性调节中起重要作用。此外,多种因素已被确定为参与控制选择性剪接,RNA的异常剪接可以导致感染、免疫疾病、免疫活动的异常以及肿瘤。本文重点讨论了AS在免疫系统细胞内的调节,以及它们对免疫生物学的影响和AS与自身免疫性疾病,如类风湿性关节炎(rheumatoid arthritis,RA)和系统性红斑狼疮(systemic lupus erythematosus,SLE)之间的关联。总结AS与自身免疫性疾病相关的部分最新发现,并试图找到剪接调节的共同模式,这可能会促进对自身免疫性疾病的理解,并开辟新的治疗途径。Alternative splicing(AS)is a general mechanism for regulating gene expression,and up to 95%of human genes experience AS,meaning that this post-transcriptional regulatory mechanism is critical for almost all cellular processes.The general function of AS is to increase the diversity of mRNA expressed from the genome.AS alters the protein encoded by mRNA,which can have profound functional effects.AS is also observed in gene products of metazoan immune systems that have evolved to effectively recognize pathogens and distinguish between"self"and"non-self",possibly thanks to the diversity and flexibility that AS provides.Human immune response is a complex process that responds to many exogenous antigens,prevents microbial infections,and monitors endogenous components of tumors and autoimmune diseases,and requires a large number of molecules to support functional complex immune activities.Alternative splicing of pre-mRNA plays an important role in immune cell development and regulation of immune activity by generating multiple transcription subtypes to supplement the function of limited genes associated with immune response.In addition,multiple factors have been identified to be involved in the control of alternative splicing,where abnormal splicing of RNA can lead to infections,immune diseases,abnormalities in immune activity,and tumors.In this review,we focus on the regulation of AS in immune system cells,their impact on immunobiology and AS and autoimmune diseases,such as rheumatoid arthritis and systemic lupus erythematosus.We summarize some of the recent findings that AS is associated with autoimmune diseases,and try to find common patterns of splicing regulation that may advance our understanding of autoimmune diseases and open up new therapeutic approaches.

关 键 词：自身免疫性疾病 可变剪接 选择性剪接 基因表达 

分 类 号：R593.2[医药卫生—内科学]