Table_1_Genome-Wide Profiling Reveals Alternative Polyadenylation of Innate Immune-Related mRNA in Patients With COVID-19.xlsx

The coronavirus disease 2019 (COVID-19) pandemic has caused many deaths worldwide. To date, the mechanism of viral immune escape remains unclear, which is a great obstacle to developing effective clinical treatment. RNA processing mechanisms, including alternative polyadenylation (APA) and alternative splicing (AS), are crucial in the regulation of most human genes in many types of infectious diseases. Because the role of APA and AS in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown, we performed de novo identification of dynamic APA sites using a public dataset of human peripheral blood mononuclear cell (PBMC) RNA-Seq data in COVID-19 patients. We found that genes with APA were enriched in innate immunity -related gene ontology categories such as neutrophil activation, regulation of the MAPK cascade and cytokine production, response to interferon-gamma and the innate immune response. We also reported genome-wide AS events and enriched viral transcription-related categories upon SARS-CoV-2 infection. Interestingly, we found that APA events may give better predictions than AS in COVID-19 patients, suggesting that APA could act as a potential therapeutic target and novel biomarker in those patients. Our study is the first to annotate genes with APA and AS in COVID-19 patients and highlights the roles of APA variation in SARS-CoV-2 infection.

新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）大流行已在全球造成大量死亡。截至目前，病毒免疫逃逸的机制仍不明确，这是开发有效临床治疗手段的一大阻碍。RNA加工机制包括可变多聚腺苷酸化（alternative polyadenylation, APA）与可变剪接（alternative splicing, AS），在多种传染病中对多数人类基因的调控发挥关键作用。鉴于APA与AS在应对严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）感染中的作用尚未明晰，本研究利用公开的COVID-19患者外周血单个核细胞（peripheral blood mononuclear cell, PBMC）RNA测序（RNA-Seq）数据集，对动态APA位点进行从头鉴定。研究发现，携带APA的基因富集于中性粒细胞激活、丝裂原活化蛋白激酶（MAPK）级联反应调控、细胞因子产生、γ干扰素应答以及固有免疫应答等与固有免疫相关的基因本体（gene ontology, GO）类别。本研究还报道了SARS-CoV-2感染后全基因组范围内的AS事件及富集的病毒转录相关功能类别。有趣的是，本研究发现APA事件相较于AS可对COVID-19患者实现更精准的预测，提示APA可作为此类患者的潜在治疗靶点与新型生物标志物。本研究首次对COVID-19患者中携带APA与AS的基因进行注释，并强调了APA变异在SARS-CoV-2感染中的作用。