Open AccessAbnormal global alternative RNA splicing in COVID-19 patients
Author(s) -
Changli Wang,
Lijun Chen,
Yaobin Chen,
Wenwen Jia,
Xunhui Cai,
Yufeng Liu,
Fenghu Ji,
Ping Xiong,
Anyi Liang,
Ren Liu,
Yuanlin Guan,
Zhongyi Cheng,
Yuhua Weng,
Weixin Wang,
Yaqi Duan,
Dong Kuang,
Sanpeng Xu,
Haodong Cai,
Xia Qin,
Dehua Yang,
Mingwei Wang,
Xun Yang,
Jianjun Zhang,
Chao Cheng,
Liang Liu,
Zhongmin Liu,
Liang Ren,
Wang Guo-pin,
Zhendong Li,
Han Xia,
Tian Xia
Publication year - 2022
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1010137
Subject(s) - transcriptome , biology , alternative splicing , rna splicing , exon , covid-19 , exon skipping , computational biology , rna , genetics , bioinformatics , gene , gene expression , medicine , disease , infectious disease (medical specialty)
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.