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Volume 101, Issue 10

A putative new SARS-CoV protein, 3c, encoded in an ORF overlapping ORF3a Open Access

Abstract

Identification of the full complement of genes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a crucial step towards gaining a fuller understanding of its molecular biology. However, short and/or overlapping genes can be difficult to detect using conventional computational approaches, whereas high-throughput experimental approaches – such as ribosome profiling – cannot distinguish translation of functional peptides from regulatory translation or translational noise. By studying regions showing enhanced conservation at synonymous sites in alignments of SARS-CoV-2 and related viruses (subgenus ) and correlating the results with the conserved presence of an open reading frame (ORF) and a plausible translation mechanism, a putative new gene – ORF3c – was identified. ORF3c overlaps ORF3a in an alternative reading frame. A recently published ribosome profiling study confirmed that ORF3c is indeed translated during infection. ORF3c is conserved across the subgenus , and encodes a 40–41 amino acid predicted transmembrane protein.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): 3c , coronavirus , ORF3c , overlapping gene , sarbecovirus and SARS-CoV
Funding
This study was supported by the:
  • H2020 European Research Council (Award 646891)
    • Principle Award Recipient: Andrew Firth
  • Wellcome Trust (Award 106207)
    • Principle Award Recipient: Andrew Firth
© 2020 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2020-07-15
2024-12-09
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References

  1. Snijder EJ, Decroly E, Ziebuhr J. The nonstructural proteins directing coronavirus RNA synthesis and processing. Adv Virus Res 2016; 96:59–126 [View Article][PubMed]
     [Google Scholar]
  2. Sola I, Almazán F, Zúñiga S, Enjuanes L. Continuous and discontinuous RNA synthesis in coronaviruses. Annu Rev Virol 2015; 2:265–288 [View Article][PubMed]
     [Google Scholar]
  3. Liu DX, Fung TS, Chong KK-L, Shukla A, Hilgenfeld R. Accessory proteins of SARS-CoV and other coronaviruses. Antiviral Res 2014; 109:97–109 [View Article][PubMed]
     [Google Scholar]
  4. Schaecher SR, Mackenzie JM, Pekosz A. The ORF7b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is expressed in virus-infected cells and incorporated into SARS-CoV particles. J Virol 2007; 81:718–731 [View Article][PubMed]
     [Google Scholar]
  5. Xu K, Zheng B-J, Zeng R, Lu W, Lin Y-P et al. Severe acute respiratory syndrome coronavirus accessory protein 9B is a virion-associated protein. Virology 2009; 388:279–285 [View Article][PubMed]
     [Google Scholar]
  6. Chinese SARS Molecular Epidemiology Consortium He J. Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Science 2004; 303:1666–1669 [View Article][PubMed]
     [Google Scholar]
  7. Finkel Y, Mizrahi O, Nachshon A, Weingarten-Gabbay S, Yahalom-Ronen Y et al. The coding capacity of SARS-CoV-2. bioRxiv 20202020.05.07.082909
     [Google Scholar]
  8. Firth AE. Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses. Nucleic Acids Res 2014; 42:12425–12439 PMID [View Article][PubMed]
     [Google Scholar]
  9. Fang Y, Treffers EE, Li Y, Tas A, Sun Z et al. Efficient -2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein. Proc Natl Acad Sci U S A 2012; 109:E2920–E2928 [View Article][PubMed]
     [Google Scholar]
  10. Jagger BW, Wise HM, Kash JC, Walters K-A, Wills NM et al. An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 2012; 337:199–204 [View Article][PubMed]
     [Google Scholar]
  11. Loughran G, Firth AE, Atkins JF. Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the Cardiovirus genome. Proc Natl Acad Sci U S A 2011; 108:E1111–E1119 [View Article][PubMed]
     [Google Scholar]
  12. Lulla V, Firth AE. A hidden gene in astroviruses encodes a cell-permeabilizing protein involved in virus release. bioRxiv 2019661579
     [Google Scholar]
  13. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990; 215:403–410 [View Article][PubMed]
     [Google Scholar]
  14. Stocsits RR, Hofacker IL, Fried C, Stadler PF. Multiple sequence alignments of partially coding nucleic acid sequences. BMC Bioinformatics 2005; 6:160 [View Article][PubMed]
     [Google Scholar]
  15. Baranov PV, Henderson CM, Anderson CB, Gesteland RF, Atkins JF et al. Programmed ribosomal frameshifting in decoding the SARS-CoV genome. Virology 2005; 332:498–510 [View Article][PubMed]
     [Google Scholar]
  16. Firth AE, Brierley I. Non-Canonical translation in RNA viruses. J Gen Virol 2012; 93:1385–1409 [View Article][PubMed]
     [Google Scholar]
  17. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 1986; 44:283–292 [View Article][PubMed]
     [Google Scholar]
  18. Käll L, Krogh A, Sonnhammer ELL. Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server. Nucleic Acids Res 2007; 35:W429–W432 [View Article][PubMed]
     [Google Scholar]
  19. Ingolia NT, Ghaemmaghami S, Newman JRS, Weissman JS. Genome-Wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 2009; 324:218–223 [View Article][PubMed]
     [Google Scholar]
  20. Irigoyen N, Firth AE, Jones JD, Chung BY-W, Siddell SG et al. High-Resolution analysis of coronavirus gene expression by RNA sequencing and ribosome profiling. PLoS Pathog 2016; 12:e1005473 [View Article][PubMed]
     [Google Scholar]
  21. Wu H-Y, Guan B-J, Su Y-P, Fan Y-H, Brian DA. Reselection of a genomic upstream open reading frame in mouse hepatitis coronavirus 5'-untranslated-region mutants. J Virol 2014; 88:846–858 [View Article][PubMed]
     [Google Scholar]
  22. Edgar RC. Muscle: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004; 5:113 [View Article][PubMed]
     [Google Scholar]
  23. Rice P, Longden I, Bleasby A. EMBOSS: the European molecular biology open software suite. Trends Genet 2000; 16:276–277 [View Article][PubMed]
     [Google Scholar]
  24. Cagliani R, Forni D, Clerici M, Sironi M. Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses. Infect Genet Evol 2020; 83:104353 [View Article][PubMed]
     [Google Scholar]
  25. Jungreis I, Sealfon R, Kellis M. Sarbecovirus comparative genomics elucidates gene content of SARS-CoV-2 and functional impact of COVID-19 pandemic mutations. bioRxiv 20202020.06.02.130955 [View Article][PubMed]
     [Google Scholar]
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A putative new SARS-CoV protein, 3c, encoded in an ORF overlapping ORF3a
J. Gen. Virol. 101, 1085 (2020); https://doi.org/10.1099/jgv.0.001469
/content/journal/jgv/10.1099/jgv.0.001469
/content/journal/jgv/10.1099/jgv.0.001469
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