Immunology Graduate Group and the Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Immunol Rev. 2021 Nov;304(1):30-50. doi: 10.1111/imr.13018. Epub 2021 Aug 8.
The latest advances in next-generation sequencing studies and transcriptomic profiling over the past decade have highlighted a surprising frequency of genes regulated by RNA processing mechanisms in the immune system. In particular, two control steps in mRNA maturation, namely alternative splicing and alternative polyadenylation, are now recognized to occur in the vast majority of human genes. Both have the potential to alter the identity of the encoded protein, as well as control protein abundance or even protein localization or association with other factors. In this review, we will provide a summary of the general mechanisms by which alternative splicing (AS) and alternative polyadenylation (APA) occur, their regulation within cells of the immune system, and their impact on immunobiology. In particular, we will focus on how control of apoptosis by AS and APA is used to tune cell fate during an immune response.
过去十年中,下一代测序研究和转录组分析的最新进展突显了 RNA 处理机制在免疫系统中调控基因的惊人频率。特别是,mRNA 成熟的两个控制步骤,即选择性剪接和可变多聚腺苷酸化,现在被认为在绝大多数人类基因中发生。这两者都有可能改变编码蛋白的身份,以及控制蛋白丰度,甚至蛋白定位或与其他因素的关联。在这篇综述中,我们将总结选择性剪接 (AS) 和可变多聚腺苷酸化 (APA) 发生的一般机制、它们在免疫系统细胞内的调节以及它们对免疫生物学的影响。特别是,我们将重点关注 AS 和 APA 通过控制细胞凋亡来调节免疫反应过程中的细胞命运。