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The genome sequence for the GenBank virus JX869059.2 (a human betacoronavirus) contains, among others, two proteins:

  • N protein (range 28566..29807) and
  • Orf8b (range 28762..29100).

The interval for Orf8b is contained in the interval for N.

How are these proteins translated? Is the orf8 protein created with post-translational processing after N is translated, or does the ribosome translate the two proteins separately?

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  • $\begingroup$ ncbi.nlm.nih.gov/nuccore/JX869059.2?report=GenBank report all proteins really build from virus or they are reported from page ncbi.nlm.nih.gov/orffinder query "JX869059.2" $\endgroup$
    – RosLuP
    Sep 18 '20 at 20:47
  • $\begingroup$ because the 28762-28566 is not divisible by 3, the title is wrong, it is not one protein inside one other, and only ribosome can compose orf8 protein in few i know...so ribosome has to compose both (N and orf8 protein, if they exist) $\endgroup$
    – RosLuP
    Sep 21 '20 at 19:05
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    $\begingroup$ Viruses are really compressed in terms of information —we've all become familiar with the single long peptide that gets chopped into functional protein by the protease of SAR-COV-2. In HIV, translational slippage gets used to make a rarer peptide (as opposed to alternative splicing say). However, whereas enzyme are generally big peptides that inhibit others (such as the MERS homologue of orf8) need only 5-10 amino acids to do the trick (like a piece of paper to fix a wobbly table). $\endgroup$ Sep 22 '20 at 8:10
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Note that the protein sequence of ORF8b is not contained within the protein sequence of protein N. That means that they are translated from different frames (though they are in the same orientation). Indeed, if we just subtract the start coordinates we do not find a multiple of 3.

Thus, they cannot be results of the same translational event. This means that the smaller protein could result from translational slippage (as suggested by Matteo Ferla), "leaky scanning" of the translation machines for start codons, or it could simply result from a different ribosome assembly site, recruited via the viral mechanism of an internal ribosome entry site, which allows a ribosome to be recruited in a mRNA cap-independent fashion (though this may be less likely).

For some mechanistic details of how one such ORF is translated, see this paper.

It looks like such things are sometimes called "subgenomic mRNAs". For a paper on such nested genes in coronavirus, including I believe Orf8b, see here.

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Essentially @MaximilianPress hit the nail on the head. sgRNA is a major feature of SARS-CoV-2.

This is where the 5' UTR is spliced at numerous locations in the genome, such that although it is a single stranded positive sense RNA genome it behaves like a segmented viral genome because it is translated as a series of sub-genomic RNA molecules. So influenza is a classic example of a segmented genome. SARS-CoV-2 is more slightly complicated because it is using frameshifts to achieve to achieve the different sgRNAs.

However it isn't a particularly strong example of frameshifts because virus such as HBV (hep B) are pass masters, where two different proteins are encoded within a single locus.

My personal view is that slippage isn't operating here, unlike say HIV, but that it is a function of the sgRNA construction, thus N protein occurs on one sgeRNA and ORF8b occurs on a second sgRNA and sg signal is within the N protein.

If SARS-CoV-2 is your thing then stuff like this is a big player in interpreting bioinformatic output.

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