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N1-methylpseudouridine is a chemically modified pyrimidine nucleoside in which a methyl group is attached at the N1 position of pseudouridine, used as a uridine analog in synthetic mRNA to enhance translational efficiency and reduce innate immune sensing. It is a natural component of archaeal tRNA and has been widely adopted in in vitro–transcribed mRNA for vaccines and therapeutics, including the SARS-CoV-2 mRNA vaccines tozinameran and elasomeran, because incorporation of N1-methylpseudouridine into mRNA blunts activation of RNA-sensing receptors such as TLR7, reduces eIF2α phosphorylation–dependent translational shutdown, stabilizes RNA secondary structure, and increases ribosome density, thereby improving protein yield and tolerability.[1][6][9]
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