Recoding by N(1)-methylpseudouridine guides rational mRNA vaccine design.

N(1)-methylpseudouridine increases +1 frameshifting on UUUC motifs in mRNA vaccines, affecting translational fidelity and antigenicity.

• Why it matters: Understanding how mRNA modifications influence translation accuracy is crucial for designing safe and effective vaccines, especially given concerns about unintended immune responses.
• What they did: The study used dual-fluorescence reporters, in vitro translation, and single-molecule FRET to analyze the effects of m 1 Ψ on frameshifting, focusing on UUUC motifs in therapeutic mRNAs.
• The result: Findings show m 1 Ψ promotes frameshifting by weakening codon-anticodon interactions, but codon optimization (e.g., replacing UUUC) can prevent this, guiding improved mRNA vaccine design.