N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting

<p>The paper investigates how incorporating modified ribonucleotides like N1-methylpseudouridine (1-methyl&Psi;) into mRNA vaccines affects their translation fidelity. They found that 1-methyl&Psi; significantly increases +1 ribosomal frameshifting during mRNA translation, resulting in mistranslated proteins. This was shown using reporter mRNAs in vitro and in cells.</p> <p>The +1 ribosomal frameshifting is likely caused by ribosome stalling during translation elongation when 1-methyl&Psi; is present. It occurs at specific &ldquo;slippery sequences&rdquo; in the mRNA. In mice and humans vaccinated with a 1-methyl&Psi;-containing mRNA vaccine (BNT162b2), T cell responses were detected against +1 frameshifted peptide products. This suggests cellular immunity can develop against mistranslated proteins.</p> <p><a href="https://medium.com/@axialxyz/n1-methylpseudouridylation-of-mrna-causes-1-ribosomal-frameshifting-ef96b2285b63"><strong>Click Here</strong></a></p>