"Methylpseudouridylation: Unraveling the Mystery of Ribosomal Frameshifting"

The presence of N1-methylpseudouridine (1-methylΨ) in mRNA can cause ribosomal frameshifting, leading to the production of +1 frameshifted polypeptides. This study investigated the effects of various modified ribonucleotides on mRNA translation and found that 1-methylΨ significantly increased frameshifting. Furthermore, it was observed that mRNA vaccines containing 1-methylΨ, such as the approved SARS-CoV-2 mRNA vaccines, can elicit off-target cellular immune responses due to the production of +1 frameshifted antigens. These findings highlight the importance of understanding the impact of modified ribonucleotides on protein synthesis and the design of mRNA-based therapeutics.