Pseudouridine occurs naturally in some RNAs. But what about the methylated variant of it, N1-methyl-pseudouridine? The latter is a key ingredient in both the Pfizer and Moderna Covid-19 vaccines, probably due to its relative "potency" in evading immunogenicity to exogenous mRNA itself and its ability to apparently put ribosomes in a sort of "overdrive". (It's use in mRNA therapeutics has been patented by Moderna in 2012 or so.)

Does N1-methyl-pseudouridine occur naturally, in particular, does it occur in RNA?


N1-methyl-pseudouridine occurs naturally in the tRNAs of most archaea. It replaces the ribothymidine found in the TΨC-loop of eubacterial and eukaryotic tRNAs.

Comparison of tRNAs

Although the enzyme responsible for the conversion of uridine to pseudouridine has been known for some time, it is only relatively recently (2012) that the gene for the methylation of the pseudouridine was reported in a paper, the introduction to which provides a useful background to the topic.

Original References

Pang, H. et al. (1962) J.Biol.Chem. 257 3589-3593
Gupta, R. (1964) J.Biol.Chem. 259 9461-9471


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