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:10.1371/journal.pgen.1010137

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 YangMing Wei Wang, Xiangping Yang, Jianjun Zhang, Chao Cheng, Liang Liu, Zhongmin Liu, Ren Liang, Guopin Wang, Zhendong Li, Han Xia, Tian Xia

Thoracic Head & Neck Medical Oncology

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e1010137
Journal	PLoS genetics
Volume	18
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1010137
State	Published - Apr 14 2022

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

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Wang, C, Chen, L, Chen, Y, Jia, W, Cai, X, Liu, Y, Ji, F, Xiong, P, Liang, A, Liu, R, Guan, Y, Cheng, Z, Weng, Y, Wang, W, Duan, Y, Kuang, D, Xu, S, Cai, H, Xia, Q, Yang, D, Wang, MW, Yang, X, Zhang, J, Cheng, C, Liu, L, Liu, Z, Liang, R, Wang, G, Li, Z, Xia, H & Xia, T 2022, 'Abnormal global alternative RNA splicing in COVID-19 patients', PLoS genetics, vol. 18, no. 4, e1010137. https://doi.org/10.1371/journal.pgen.1010137

@article{50b738641e0e48429047cc7c956e112b,

title = "Abnormal global alternative RNA splicing in COVID-19 patients",

abstract = "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.",

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

note = "Funding Information: This work was supported by the Ministry of Science and Technology of P. R. China Plan (grant number 2020YFC0844700). T.X. is supported by the National Natural Science Foundation of China (61571202). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank all the healthcare workers who fight SARS-CoV-2 on the front line. We also thank Wen Wang for their feedback on the manuscript. Publisher Copyright: Copyright: {\textcopyright} 2022 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2022",

month = apr,

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doi = "10.1371/journal.pgen.1010137",

language = "English (US)",

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T1 - Abnormal global alternative RNA splicing in COVID-19 patients

AU - Wang, Changli

AU - Chen, Lijun

AU - Chen, Yaobin

AU - Jia, Wenwen

AU - Cai, Xunhui

AU - Liu, Yufeng

AU - Ji, Fenghu

AU - Xiong, Peng

AU - Liang, Anyi

AU - Liu, Ren

AU - Guan, Yuanlin

AU - Cheng, Zhongyi

AU - Weng, Yejing

AU - Wang, Weixin

AU - Duan, Yaqi

AU - Kuang, Dong

AU - Xu, Sanpeng

AU - Cai, Hanghang

AU - Xia, Qin

AU - Yang, Dehua

AU - Wang, Ming Wei

AU - Yang, Xiangping

AU - Zhang, Jianjun

AU - Cheng, Chao

AU - Liu, Liang

AU - Liu, Zhongmin

AU - Liang, Ren

AU - Wang, Guopin

AU - Li, Zhendong

AU - Xia, Han

AU - Xia, Tian

N1 - Funding Information: This work was supported by the Ministry of Science and Technology of P. R. China Plan (grant number 2020YFC0844700). T.X. is supported by the National Natural Science Foundation of China (61571202). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank all the healthcare workers who fight SARS-CoV-2 on the front line. We also thank Wen Wang for their feedback on the manuscript. Publisher Copyright: Copyright: © 2022 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/4/14

Y1 - 2022/4/14

N2 - 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.

AB - 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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DO - 10.1371/journal.pgen.1010137

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VL - 18

JO - PLoS genetics

JF - PLoS genetics

IS - 4

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ER -

Abnormal global alternative RNA splicing in COVID-19 patients

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