Because of the possibility of ‘wobble’ in the base-pair made between the third (5’) position of the anticodon and the third (3’) base of the the mRNA codon , single tRNAs with appropriate bases in this position are often employed by the cell to decode more than one codon specifying the same amino acid (synonymous codons). This is not possible and does not occur in the first or second positions of the codon.

N1-methyl-pseudouridine has been used to replace uracil in the preparation of mRNA for vaccines because it renders the mRNA less immunogenic. It has the same potential for base–pairing as uracil, so that even if its orientation in space is not absolutely identical, one would expect it to be able to form a base-pair with the wobble position of the appropriate anticodon.

But what is the situation with N1-methyl-pseudouridine at the first or second codon positions, where base-pairing is more stringent? Is there a potential for miscoding there, producing a proteins with incorrect amino acids?

  • $\begingroup$ Welcome to Biology.SE. The Biology.SE community has agreed that questions that show little or no prior research effort are off-topic on this site as are "homework" questions unless you have shown your attempt at an answer. Please edit your question and tell us where you've looked for answers, what you do know about the topic, and where exactly you still have questions. Under researched questions may be subject to down-voting and closure. Please take the tour and consult the help center starting with How to Ask for details. $\endgroup$
    – tyersome
    Sep 16 '21 at 20:33
  • 3
    $\begingroup$ Welcome to SE Biology. It is the practice here to allow editing of questions (and answers), although the poster can revert them, in order to improve them. I have done this to your question to make the chemistry and logic more precise. Please do not regard this in a negative fashion. On another quite different point I would ask you to think about how these modified mRNAs are made and whether they work or not. That may help you to answer your own question. $\endgroup$
    – David
    Sep 16 '21 at 23:41
  • $\begingroup$ Have you looked at any space filled models for this? You can start to see how the wobble works, and then I think you can start to answer your question yourself as others have stated. $\endgroup$
    – Atl LED
    Sep 17 '21 at 3:04
  • $\begingroup$ @AtlLED — How are you suggesting this be modelled exactly — onto what published structure using what software? And why spacefilling — one seldom sees spacefilling models of nucleic acid hybrids, except to give an overall impression of the shape of a molecule? Distances and angles are what is important, but to measure these one has to know whether and to what extent the bonding atoms in N1-methyl-pseudouridine are displaced from those in U. Not quite so simple. $\endgroup$
    – David
    Sep 17 '21 at 8:54
  • $\begingroup$ This paper says "all U nucleotides were replaced by N1-methylpseudouridine (Ψ). However, Ψ wobbles more in base-pairing than U and can pair not only with A and G, but also, to a lesser extent, with C and U. This is likely to increase misreading of a codon by a near-cognate tRNA." However, this paper says "N1-methyl-Ψ can only use its Watson-Crick face to base-pair with another nucleoside, thus preventing it from wobble-pairing with other nucleotides (G, U, and C)." $\endgroup$
    – endolith
    Jan 10 at 18:30

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