PLoS Genetics (Apr 2022)

Abnormal global alternative RNA splicing in COVID-19 patients.

  • Changli Wang,
  • Lijun Chen,
  • Yaobin Chen,
  • Wenwen Jia,
  • Xunhui Cai,
  • Yufeng Liu,
  • Fenghu Ji,
  • Peng Xiong,
  • Anyi Liang,
  • Ren Liu,
  • Yuanlin Guan,
  • Zhongyi Cheng,
  • Yejing Weng,
  • Weixin Wang,
  • Yaqi Duan,
  • Dong Kuang,
  • Sanpeng Xu,
  • Hanghang Cai,
  • Qin Xia,
  • Dehua Yang,
  • Ming-Wei Wang,
  • Xiangping Yang,
  • Jianjun Zhang,
  • Chao Cheng,
  • Liang Liu,
  • Zhongmin Liu,
  • Ren Liang,
  • Guopin Wang,
  • Zhendong Li,
  • Han Xia,
  • Tian Xia

DOI
https://doi.org/10.1371/journal.pgen.1010137
Journal volume & issue
Vol. 18, no. 4
p. e1010137

Abstract

Read online

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.