N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation.

ABSTRACT: The ribosome utilizes hydrogen bonding between mRNA codons and aminoacyl-tRNAs to ensure rapid and accurate protein production. Chemical modification of mRNA nucleobases can adjust the strength and pattern of this hydrogen bonding to alter protein synthesis. We investigate how the N1-methylpseudouridine (m¹Ψ) modification, commonly incorporated into therapeutic and vaccine mRNA sequences, influences the speed and fidelity of translation. We find that m¹Ψ does not substantially change the rate constants for amino acid addition by cognate tRNAs or termination by release factors. However, we also find that m¹Ψ can subtly modulate the fidelity of amino acid incorporation in a codon-position and tRNA dependent manner in vitro and in human cells. Our computationa

SUBMITTER: Monroe J 

PROVIDER: S-EPMC11405884 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature