Yaara Finkel, Orel Mizrahi, Aharon Nachshon, Shira Weingarten-Gabbay, David Morgenstern, Yfat Yahalom-Ronen, Hadas Tamir, Hagit Achdout, Dana Stein, Ofir Israeli, Adi Beth-Din, Sharon Melamed, Shay Weiss, Tomer Israely, Nir Paran, Michal Schwartz, Noam Stern-Ginossar
Author Information
Yaara Finkel: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. ORCID
Orel Mizrahi: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Aharon Nachshon: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Shira Weingarten-Gabbay: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
David Morgenstern: de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalised Medicine, Weizmann Institute of Science, Rehovot, Israel.
Yfat Yahalom-Ronen: Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Hadas Tamir: Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Hagit Achdout: Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Dana Stein: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Ofir Israeli: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Adi Beth-Din: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Sharon Melamed: Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Shay Weiss: Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Tomer Israely: Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Nir Paran: Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Michal Schwartz: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. ORCID
Noam Stern-Ginossar: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. noam.stern-ginossar@weizmann.ac.il. ORCID
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. 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, 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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