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]
| Orf10 protein, SARS-CoV-2 | |
|---|---|
| Identifiers | |
| Symbol | Orf10_SARS-CoV-2 |
| InterPro | IPR044342 |
Properties edit
ORF10 is located downstream of the N gene, which encodes coronavirus nucleocapsid protein. It is the annotated open reading frame furthest to the 3' end of the genome. It encodes a 38-amino acid hypothetical protein.[1]
Expression and function edit
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 edit
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 edit
- ^ a b 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.
- ^ 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.
- ^ a b 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.
- ^ a b c d 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b 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.