Abnormal global alternative RNA splicing in COVID-19 patients

作者：Changli Wang, Lijun Chen, Yaobin Chen, Wenwen Jia, Xunhui Cai, Yufeng Liu, Fenghu Ji, Xiong Peng, Anyi Liang, Ren Liu, Yuanlin Guan, Zhongyi Cheng, Yejing Weng, Weixin Wang, Yaqi Duan, Dong Kuang, Sanpeng Xu, Hanghang Cai, Xia Qin, Dehua Yang, Mingwei Wang, Xiang‐Ping Yang, Jianjun Zhang, Chao Cheng, Liang Liu, Zhongmin Liu, Ren Liang, Guopin Wang, Zhendong Li, Han Xia, Tian Xia · 发表于：PLoS Genetics · 年份：2022 · DOI：10.1371/journal.pgen.1010137 · 被引用次数：42 · 研究领域：RNA Research and Splicing、RNA modifications and cancer、RNA regulation and disease

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.