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.
【초록키워드】 COVID-19, Transcriptome, SARS-CoV-2, therapy, SARS-COV-2 infection, neutrophil, Infection, Blood coagulation, viral infections, COVID-19 diagnosis, RNA splicing, antiviral immunity, expression, Intensive, transcriptome analysis, proteomic, cytokine production, COVID-19 patients, Clinical severity, Analysis, COVID-19 patient, neutrophil activation, dysregulation, domain, severe COVID-19 patients, transcripts, sequencing data, ExoN, therapeutic activity, systematic analysis, CD74, host transcriptome, transcript, Host, transcriptomic, widespread, Alter, highlight, LRRFIP1, reduced, functional, changes in, contribute, correlated, induce, affecting, disrupt, down-regulated, severe COVID-19 patient, 【제목키워드】 COVID-19 patient,