Key result
N1-methylpseudouridine (m1Ψ) modified mRNA did not significantly alter decoding accuracy or increase miscoded peptides in cell culture compared with unmodified mRNA.
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Why the study?
Relatively few studies have addressed the effects of modified nucleotides such as N1-methylpseudouridine on the decoding process during translation.
Does mRNA containing N1-methylpseudouridine alter translation fidelity compared to unmodified mRNA in cell culture and reconstituted systems?
Does mRNA containing N1-methylpseudouridine alter translation fidelity compared to unmodified mRNA in cell culture and reconstituted systems?
N1-methylpseudouridine modification in mRNA vaccines does not significantly impact translational fidelity, supporting the safety and efficacy of future RNA therapeutics.
Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the technology is the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) to decrease immunogenicity of the RNA. However, relatively few studies have addressed the effects of modified nucleotides on the decoding process. Here, we investigate the effect of m1Ψ and the related modification pseudouridine (Ψ) on translation. In a reconstituted system, we find that m1Ψ does not significantly alter decoding accuracy. More importantly, we do not detect an increase in miscoded peptides when mRNA containing m1Ψ is translated in cell culture, compared with unmodified mRNA. We also find that m1Ψ does not stabilize mismatched RNA-duplex formation and only marginally promotes errors during reverse transcription. Overall, our results suggest that m1Ψ does not significantly impact translational fidelity, a welcome sign for future RNA therapeutics.
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Kim et al. (2022) studied this question. N1-methylpseudouridine (m1Ψ) modified mRNA vs. Unmodified mRNA was evaluated on Translational fidelity and decoding accuracy. N1-methylpseudouridine (m1Ψ) modified mRNA did not significantly alter decoding accuracy or increase miscoded peptides in cell culture compared with unmodified mRNA.
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