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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses subgenomic RNA (sgRNA) to produce viral proteins for replication and immune evasion. We apply long-read RNA and cDNA sequencing to in vitro human and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA upregulates earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of open reading frame 1ab (ORF1ab) containing nsp1 joins to ORF10, and the 3' untranslated region (UTR) upregulates at 48 h post-infection in human cell lines. We identify double-junction sgRNA containing both TRS-dependent and -independent junctions. We find multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA and that sgRNA modifications are stable across transcript clusters, host cells, and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle.

Original publication




Journal article


Cell Rep

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COVID-19, Nanopore sequencing, RNA modification, SARS-CoV-2, coronavirus, differential expression, direct RNA sequencing, direct cDNA sequencing, discontinuous transcription, poly(A) tail, Animals, COVID-19, Caco-2 Cells, Cell Line, Chlorocebus aethiops, Epigenesis, Genetic, Genome, Viral, Humans, Immune Evasion, Open Reading Frames, RNA, Viral, SARS-CoV-2, Transcription, Genetic, Transcriptome, Vero Cells, Viral Proteins