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According to the WHO submission and one of the preprints from BioNTech/Pfizer, the 3'UTR of their Covid-19 vaccine's mRNA is the combo of the AES and mtRNR1 sequences, which (in the preprint) BioNTech cites to a paper on library screening of 3'UTRs that achieve high mRNA stability etc.

But as far as as I can tell, BioNTech added a "CUC GAG" between the (doubled) stop codon and the beginning of the AES as it's given in Supplementary Table 3 of the library paper cited, i.e. the actual AES starts with CUG GUA CUG, or more precisely using the global Ψ substitution as given in the WHO submission, the sequence starting with the stop codon(s) is:

ΨGA ΨGA CΨC GAG CΨG GΨA CΨG CAΨ GCA

So, what's the point of the bolded "glue" CUC GAG?

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    $\begingroup$ There is also this part at the end ACCCTGGAGCTAGCAAAAAAAAA... $\endgroup$
    – reuns
    Jan 4, 2021 at 3:57
  • $\begingroup$ @reuns: FWTW, they did not add any glue in between the AES and mtRNR1 sequences (which form the "double UTR" as they call it) GACACCΨCC CAAGCACGC. $\endgroup$ Jan 4, 2021 at 11:39
  • $\begingroup$ The final part of mtRNR1 has something appended though compared to the library paper (it ends with AGCCACACC in supp. table 3), but in the WHO doc it has AGC CAC ACC CΨG GAG CΨA GCA AAAAA $\endgroup$ Jan 4, 2021 at 11:45
  • $\begingroup$ Looking at the library paper more closely they, speak of a "motive core area" and "flanking areas" so these might be the latter, and were perhaps not interesting enough to publish at the time. $\endgroup$ Jan 4, 2021 at 11:54
  • $\begingroup$ I think your linked article explains perfectly how they came with the 3'UTR. I am not too worried that there is a 15+6 nucleotide difference with the vaccine as they didn't show exactly how they are mixing two 3'UTR. If you really really want to know you can try asking directly to Kariko on twitter. $\endgroup$
    – reuns
    Jan 4, 2021 at 13:26

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