N1-Methylpseudouridine (abbreviated m1Ψ) is a natural archaeal tRNA component,[1] and "hypermodified" pyrimidine nucleoside used in biochemistry and molecular biology for in vitro transcription and is found in the SARS-CoV-2 mRNA vaccines tozinameran (Pfizer–BioNTech) and elasomeran (Moderna).

[3][4] In vertebrates, it stimulates significantly less activation of the innate immune response compared to uridine,[5] while the translation is stronger.

[9] While pseudouridine can wobble-pair with bases other than A,[10] work examining COVID-19 modRNA vaccines that replace all their uridines with N1-methylpseudouridine show faithful protein production.

[11] More recent work from Mulroney and colleagues has identified that N1-methylpseudouridine can give rise to slippery sequences that promote ribosomal frameshifting.

The frameshifting is not known to contribute to any safety issues with regard to current mRNA vaccines, nor has it been shown to limit their effectiveness.