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Open reading frame found in the genome of the SARS-CoV-2 coronavirus
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]
Properties
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
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
^
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 .