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Wang, Changli; Chen, Lijun; Chen, Yaobin; Jia, Wenwen; Cai, Xunhui; Liu, Yufeng; Ji, Fenghu; Xiong, Peng; Liang, Anyi; Liu, Ren; Guan, Yuanlin; Cheng, Zhongyi; Weng, Yejing; Wang, Weixin; Duan, Yaqi; Kuang, Dong; Xu, Sanpeng; Cai, Hanghang; Xia, Qin; Yang, Dehua; Wang, Ming-Wei; Yang, Xiangping; Zhang, Jianjun; Cheng, Chao; Liu, Liang; Liu, Zhongmin; Liang, Ren; Wang, Guopin; Li, Zhendong; Xia, Han; Xia, Tian
PLOS genetics, 04/2022, Volume: 18, Issue: 4Journal Article
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.
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