可变剪接在自身免疫性疾病中的研究进展

储依然; 徐胜前

doi:10.16766/j.cnki.issn.1674-4152.003086

可变剪接在自身免疫性疾病中的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.003086

储依然,
徐胜前^,

安徽医科大学第一附属医院风湿免疫科，安徽合肥 230022

基金项目:

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

详细信息

通讯作者:
徐胜前，E-mail：xsqian-1112@163.com

中图分类号: R593.2
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- 文章访问数: 234
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- 被引次数: 0
出版历程
- 收稿日期: 2022-03-06
- 网络出版日期: 2023-08-28

Research progress of alternative splicing in autoimmune diseases

CHU Yiran,
XU Shengqian^,

Department of Rheumatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China

摘要

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。
- 自身免疫性疾病 /
- 可变剪接 /
- 选择性剪接 /
- 基因表达
Abstract: 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.
- Autoimmune diseases /
- Alternative splicing /
- Alternative splicing /
- Gene expression

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表 1 自身免疫性疾病相关的可变剪接基因

Table 1. Variable splicing genes associated with autoimmune diseases

自身免疫性疾病	基因	剪接亚型
类风湿性关节炎	FOXP3	FOXP3fl、FOXP3D2
	CD44	CD44v3、v4、v7-v8
	Fibronectin	含EDA区的亚型
	IL6R	可溶性受体
	TNFR2(跳过外显子7、8)	新型可溶性受体
	Tenascin-C	大异构体增加
	CD1d(跳过外显子4、5)	可溶性受体
系统性红斑狼疮	CD44	CD44v6亚型
	RasGRP1	异常剪接变异体
	IRF5(替代5’剪接位点)	特异性外显子1
	CD72	缺失外显子8的亚型
	BANK1(分支点SNP)	缺失外显子2的亚型
	LILRA2(替代3’剪接位点)	缺乏3个氨基酸的新异构体
硬皮病	IL4	短异构体
溃疡性结肠炎	PTPσ(跳过外显子8、9)	缺乏ig样结构域的亚型
多发性硬化	IL7R(外显子6的跳过)	产生更多的sIL7R
	OAS1(替代3’剪接位点)	新的异构体
	MBP	多种异构体
	MOG	多种异构体
	PLP(替代5’剪接位点)	两种亚型
注：Fibronectin为纤连蛋白；EDA为额外域A；IL6R为白细胞介素6受体；TNFR2为肿瘤坏死因子α2受体；Tenascin-C为肌腱蛋白C；RasGRP1为鸟苷酸释放蛋白1；IRF5为干扰素调节因子5；BANK1为具有锚蛋白重复序列的B细胞支架蛋白；LILRA2为白细胞免疫球蛋白样受体A2；PTPσ为蛋白酪氨酸磷酸酶σ；IL7R为白细胞介素7受体；OAS1为2’, 5’-寡腺苷酸合成酶1；MBP为髓鞘碱性蛋白；MOG为髓鞘少突胶质糖蛋白；PLP为蛋白脂质蛋白。

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