ORF10

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Orf10 protein, SARS-CoV-2
Identifiers
SymbolOrf10_SARS-CoV-2
InterPro IPR044342

ORF10 is an open reading frame (ORF) found in the genome of the SARS-CoV-2 coronavirus. It is 38 codons long. [1] It is not conserved in all Sarbecoviruses (including SARS-CoV). In studies prompted by the COVID-19 pandemic, ORF10 attracted research interest as one of two viral accessory protein genes not conserved between SARS-CoV and SARS-CoV-2 [2] and was initially described as a protein-coding gene likely under positive selection. [3] However, although it is sometimes included in lists of SARS-CoV-2 accessory genes, experimental and bioinformatics evidence suggests ORF10 is likely not a functional protein-coding gene. [4]

Contents

Properties

ORF10 is located downstream of the N gene, which encodes coronavirus nucleocapsid protein. It is the annotated open reading frame closest to the 3' end of the genome. It encodes a 38-amino acid hypothetical protein. [1]

Expression and function

It is unlikely that ORF10 is translated under natural conditions, since subgenomic RNA containing the ORF10 region is not detected, though there is some ribosome footprinting signal. [5] When experimentally overexpressed, the ORF10 protein has been reported to interact with ZYG11B and its cullin-RING ligase protein complex. [6] However, this interaction has been shown to be dispensable in in vitro studies of the viral life cycle. [7]

Evolution

Some studies of SARS-CoV-2 genomes have described ORF10 as likely to be functional and under positive selection. [3] However, premature stop codons have been identified in SARS-CoV-2 variants [8] and in many Sarbecovirus sequences, suggesting that the putative protein product is not essential for viral replication. [4] Loss of ORF10 has also shown no effect on replication under experimental conditions in vitro . [8] It has been suggested through bioinformatics analysis that apparent sequence conservation in SARS-CoV-2 ORF10 may not be due to a protein-coding function, but instead due to conserved RNA secondary structure in the region. [4] The conserved region, which extends beyond ORF10 itself, overlaps with the coronavirus 3' UTR pseudoknot region, a secondary structure known to be involved in genome replication. [4]

References

  1. 1 2 Redondo N, Zaldívar-López S, Garrido JJ, Montoya M (7 July 2021). "SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns". Frontiers in Immunology. 12 708264. doi: 10.3389/fimmu.2021.708264 . PMC   8293742 . PMID   34305949.
  2. ↑ Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L, et al. (February 2020). "Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV". Viruses. 12 (2): 244. doi: 10.3390/v12020244 . PMC   7077191 . PMID   32098422.
  3. 1 2 Cagliani R, Forni D, Clerici M, Sironi M (September 2020). "Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses". Infection, Genetics and Evolution. 83 104353. Bibcode:2020InfGE..8304353C. doi:10.1016/j.meegid.2020.104353. PMC   7199688 . PMID   32387562.
  4. 1 2 3 4 Jungreis I, Sealfon R, Kellis M (May 2021). "SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes". Nature Communications. 12 (1): 2642. Bibcode:2021NatCo..12.2642J. doi:10.1038/s41467-021-22905-7. PMC   8113528 . PMID   33976134.
  5. ↑ Finkel Y, Mizrahi O, Nachshon A, Weingarten-Gabbay S, Morgenstern D, Yahalom-Ronen Y, et al. (January 2021). "The coding capacity of SARS-CoV-2". Nature. 589 (7840): 125–130. Bibcode:2021Natur.589..125F. doi: 10.1038/s41586-020-2739-1 . PMID   32906143. S2CID   221624633.
  6. ↑ Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. (July 2020). "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing". Nature. 583 (7816): 459–468. Bibcode:2020Natur.583..459G. doi:10.1038/s41586-020-2286-9. PMC   7431030 . PMID   32353859.
  7. ↑ Mena EL, Donahue CJ, Vaites LP, Li J, Rona G, O'Leary C, et al. (April 2021). "ORF10-Cullin-2-ZYG11B complex is not required for SARS-CoV-2 infection". Proceedings of the National Academy of Sciences of the United States of America. 118 (17) e2023157118. Bibcode:2021PNAS..11823157M. doi: 10.1073/pnas.2023157118 . PMC   8092598 . PMID   33827988.
  8. 1 2 Pancer K, Milewska A, Owczarek K, Dabrowska A, Kowalski M, Łabaj PP, et al. (December 2020). "The SARS-CoV-2 ORF10 is not essential in vitro or in vivo in humans". PLOS Pathogens. 16 (12) e1008959. doi: 10.1371/journal.ppat.1008959 . PMC   7755277 . PMID   33301543.
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