The coding capacity of SARS-CoV-2
Open accessPublished version of a preprint
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic 1. To understand the pathogenicity and antigenic potential of SARS-CoV-2 and to develop therapeutic tools, it is essential to profile the full repertoire of its expressed proteins. The current map of SARS-CoV-2 coding capacity is based on computational predictions and relies on homology with other coronaviruses. As the protein complement varies among coronaviruses, especially in regard to the variety of accessory proteins, it is crucial to characterize the specific range of SARS-CoV-2 proteins in an unbiased and open-ended manner. Here, using a suite of ribosome-profiling techniques 2-4, we present a high-resolution map of coding regions in the SARS-CoV-2 genome, which enables us to accurately quantify the expression of canonical viral open reading frames (ORFs) and to identify 23 unannotated viral ORFs. These ORFs include upstream ORFs that are likely to have a regulatory role, several in-frame internal ORFs within existing ORFs, resulting in N-terminally truncated products, as well as internal out-of-frame ORFs, which generate novel polypeptides. We further show that viral mRNAs are not translated more efficiently than host mRNAs; instead, virus translation dominates host translation because of the high levels of viral transcripts. Our work provides a resource that will form the basis of future functional studies.
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There is little evidence that ORF10 and ORF14 have functional relevance.
“However, there is little evidence of the functional relevance of ORF10 and ORF14 26,27 .”
From Spread of a SARS-CoV-2 variant through Europe in the summer of 2020 (2021) · cites this paper as [26]
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- Authors
- Finkel, Y., Mizrahi, O., Nachshon, A., Weingarten-Gabbay, S., Morgenstern, D., Yahalom-Ronen, Y., Tamir, H., Achdout, H., Stein, D., Israeli, O., Beth-Din, A., Melamed, S., Weiss, S., Israely, T., Paran, N., Schwartz, M., & Stern-Ginossar, N.
- Affiliations
- Weizmann Institute of Science (IL)
- Broad Institute (US)
- Israel Institute for Biological Research (IL)
- ORCID
- Venue
- Nature
- Published
- 2020-09-09
- Volume
- 589
- Issue
- 7840
- Pages
- 125-130
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3084071750
- Cited by
- 644
- References
- 35
- Citations by year
- 2026: 45 · 2025: 60 · 2024: 79 · 2023: 108 · 2022: 149 · 2021: 165 · 2020: 34 · 2019: 1 · 2018: 3
- FWCI
- 14.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Israel Science Foundation (1526/18)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, ribosome profiling, viral protein expression, viral protein synthesis, upstream open reading frames, viral transcriptome
- MeSH terms
- SARS-CoV-2, Animals, Cell Line, Humans, Peptides, Ribosomes, RNA, Messenger, RNA, Viral, Protein Biosynthesis, Viral Proteins, Open Reading Frames, Genome, Viral, Gene Expression Profiling, Molecular Sequence Annotation
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