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In PLoS genetics ; h5-index 96.0

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.

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