The Architecture of SARS-CoV-2 Transcriptome
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Abstract
SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3' tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.
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The discontinuous mechanism of coronavirus transcription is confirmed by sequencing the subgenomic RNAs from cultured viruses.
“This discontinuous mechanism of transcription [26,61] is confirmed by sequencing the subgenomic RNAs from cultured viruses (Figure 4C).”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [61]
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- Authors
- Kim, D., Lee, J.-Y., Yang, J.-S., Kim, J. W., Kim, V. N., & Chang, H.
- Affiliations
- Korea National Institute of Health (KR)
- Seoul National University (KR)
- Corresponding author
- Kim, V. Narry
- Chang, Hyeshik
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 181
- Issue
- 4
- Pages
- 914-921.e10
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7179501
- OpenAlex
- W3017680297
- Cited by
- 2,123
- References
- 4
- Citations by year
- 2026: 94 · 2025: 150 · 2024: 225 · 2023: 278 · 2022: 449 · 2021: 604 · 2020: 320 · 2019: 2
- FWCI
- 52.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Seoul National University
- Korea Centers for Disease Control and Prevention (19-NG044, 4845-300)
- Ministry of Science, ICT and Future Planning
- Ministry of Education
- Ministry of Science and ICT, South Korea (IBS-R008-D1)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- SARS-CoV-2, viral transcriptome, epitranscriptome, RNA modification, subgenomic RNA, discontinuous transcription, alternative splicing, open reading frames, poly(A) tail, nanopore direct RNA sequencing, viral life cycle
- MeSH terms
- Betacoronavirus, SARS-CoV-2, Animals, Chlorocebus aethiops, RNA Processing, Post-Transcriptional, RNA, Viral, Vero Cells, Sequence Analysis, RNA, Epigenesis, Genetic, Transcriptome
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