Haddox Samuel, Wu Ping, Singh Sandeep, Qin Fujun, Engel Jack, Kian Andrea, Ahmad Syed, Li Hui, Wu Peng
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Genes Dis. 2024 Jun 6;12(3):101348. doi: 10.1016/j.gendis.2024.101348. eCollection 2025 May.
Despite the availability of efficacious vaccines, COVID-19 persists and our knowledge of how SARS-CoV-2 infection affects host transcriptomics remains incomplete. Transcriptome analysis, which has progressed our understanding of the patient response to SARS-CoV-2 infection, can be enhanced by considering chimeric transcript expression. Here we assess and characterize chimeric RNAs found in the whole blood of 178 COVID-19 patients. STAR-Fusion, SOAPfuse, and EricScript were used to detect chimeric RNAs resulting in over 30,000 predictions with approximately 500 high-confidence predictions that were found by more than one software and filtered based on exon annotations around the chimeric splice junction. GO term enrichment performed on the 5' and 3' parental genes of chimeric RNAs found in severe and critical patients resulted in pathways known to be affected in these patients, such as erythroid differentiation. Motif enrichment analysis of sequences proximal to chimeric splice junctions found in COVID-19 patients versus those found in GTEx whole blood revealed two RNA binding proteins previously implicated with coronavirus infection, PTBP1 and SFPQ. We discovered a chimeric RNA that correlated with COVID-19 disease status and appeared to be dependent upon a loss of PTBP1's function as a splicing repressor. Overall, we found over 350 novel COVID-19-specific chimeric RNAs not detectable in GTEx whole blood that may also serve as biomarkers for viral infection.
尽管有有效的疫苗，但新冠病毒仍在持续传播，我们对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染如何影响宿主转录组学的了解仍不完整。转录组分析有助于我们理解患者对SARS-CoV-2感染的反应，考虑嵌合转录本表达可增强这种分析。在此，我们评估并鉴定了178例新冠患者全血中发现的嵌合RNA。使用STAR-Fusion、SOAPfuse和EricScript检测嵌合RNA，得到了超过30000个预测结果，其中约500个高可信度预测结果由多个软件发现，并根据嵌合剪接位点周围的外显子注释进行了筛选。对重症和危重症患者中发现的嵌合RNA的5'和3'亲本基因进行基因本体（GO）术语富集分析，结果显示这些患者中已知受影响的通路，如红细胞分化。对新冠患者与基因型组织表达（GTEx）全血中发现的嵌合剪接位点附近序列进行基序富集分析，发现了两种先前与冠状病毒感染有关的RNA结合蛋白，即多聚嘧啶结合蛋白1（PTBP1）和剪切因子多聚嘧啶结合蛋白相关剪接因子（SFPQ）。我们发现了一种与新冠疾病状态相关的嵌合RNA，它似乎依赖于PTBP1作为剪接抑制因子功能的丧失。总体而言，我们发现了350多种在GTEx全血中无法检测到的新型新冠病毒特异性嵌合RNA，它们也可能作为病毒感染的生物标志物。
