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人类干扰素通过转子子异能化信号传递的调节

Giulia Irene Maria Pasquesi^1,2, Holly Allen¹, Atma Ivancevic¹

¹BioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO, 80309.

bioRxiv : the preprint server for biology

|September 25, 2023

概括

可移植的元素通过替代拼接来调节人类免疫信号. 一种转子子衍生型I型干扰素受体 (IFNAR2) 的变体作为诱,抑制免疫反应,包括针对SARS-CoV-2.

科学领域:

遗传学是一个遗传学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

天生的免疫信号对于宿主防御至关重要,但需要严格监管,以防止有害的炎症和自身免疫.
替代拼接是产生蛋白质多样性和调节基因表达的关键机制.

研究的目的:

研究可移植元素在调节人体细胞内天生的免疫信号传递中的作用.
通过转子子子异能化产生的免疫基因的功能性蛋白质变体的识别.

主要方法:

对长时间读取的转录组数据集的分析,以确定转位子异能化事件.
免疫基因的转子子衍生异型的表征,包括I型干扰素受体 (IFNAR2).
功能性测试以评估转子子衍生IFNAR2异型在干扰素信号传递中的抑制作用,包括在SARS-CoV-2感染细胞中.

主要成果:

确定了许多转子子体外化事件,创造了免疫基因的预测功能蛋白质变体.
一种灵长类动物特异的,转子子衍生的IFNAR2异型在人类组织中高度表达.
这种IFNAR2变体作为一种强大的诱受体,抑制I型干扰素信号传递,即使在对SARS-CoV-2感染的反应中也是如此.

结论:

可转移元素衍生的外基子的替代拼接是控制人类先天免疫信号的重要机制.
转子子异位化已经被采用,以产生灵长类动物特有的干扰素信号的调节轴.
确定了诱受体机制,为免疫调节和潜在的治疗策略提供了新的见解.

关键词:

替代性拼接是一种替代性的拼接.这是先天免疫力.可转移的元素可以转移.第一种类型的IFN IFN.

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