Landscape of chimeric RNAs in COVID-19 patient blood  

作　　者：Samuel Haddox Ping Wu Sandeep Singh Fujun Qin Jack Engel Andrea Kian Syed Ahmad Hui Li Peng Wu 

机构地区：[1]Department of Biochemistry and Molecular Genetics,School of Medicine,University of Virginia,Charlottesville,VA 22908,USA [2]Department of Gynecology and Obstetrics,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [3]National Clinical Research Center for Gynecology and Obstetrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [4]Cancer Biology Research Center(Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [5]Computational Toxicology Facility,CSIR-Indian Institute of Toxicology Research,Lucknow,Uttar Pradesh 226001,India [6]School of Basic Medical Sciences,Academy of Medical Sciences,Zhengzhou University,Zhengzhou,Henan 450001,China [7]Department of Pathology,School of Medicine,University of Virginia,Charlottesville,VA 22908,USA

出　　处：《Genes & Diseases》2025年第3期599-610,共12页基因与疾病(英文)

基　　金：supported by the National Institutes of Health(USA)(No.R01GM132138 to H.L.).

摘　　要：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-2infection, can be enhanced by considering chimeric transcript expression. Here we assess andcharacterize 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 onesoftware and filtered based on exon annotations around the chimeric splice junction. GO termenrichment performed on the 5' and 3' parental genes of chimeric RNAs found in severe andcritical patients resulted in pathways known to be affected in these patients, such as erythroiddifferentiation. 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 bindingproteins previously implicated with coronavirus infection, PTBP1 and SFPQ. We discovered achimeric RNA that correlated with COVID-19 disease status and appeared to be dependentupon 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.

关 键 词：BLOOD Chimeric RNA COVID-19 PTBP1 SARS-CoV-2 

分 类 号：R563.1[医药卫生—呼吸系统]