Bioactivity | N1-methyl-pseudouridine (1-Methylpseudouridine), a methylpseudouridine, outperforms 5 mC and 5 mC/N1-methyl-pseudouridine in translation. N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density[1]. | ||||||||||||
Invitro | Incorporation of N1-methyl-pseudouridine into mRNA modifies mRNAs produced higher amounts of luc than the standard Luc mRNA in HEK293T cells. Incorporation of N1-methyl-pseudouridine nucleoside modification in both Luc and GFP mRNA enhances the initiation step of translation, in part by suppressing eIF2α phosphorylation. In addition, polysome formation and growth on the NN1-methyl-pseudouridine-containing Luc mRNA is enhanced due to the reduction of elongation rate. In all the in vitro translation systems, incorporation of N1-methyl-pseudouridine in Luc and GFP mRNAs dramatically enhanced translation. The N1-methyl-pseudouridine-Luc mRNA is associated with heavier polysomes than Luc mRNA[1]. | ||||||||||||
In Vivo | N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice[2].N1-methyl-pseudouridine (1-Methylpseudouridine) (20 μg; I.m. or i.d. routes for 21 days) and m5C/ N1-methyl-pseudouridine-modified mRNA respectively have a higher translational capacity than Ψ and m5C/Ψ-modified mRNA in vivo[2]. Animal Model: | ||||||||||||
Name | N1-Methylpseudouridine | ||||||||||||
CAS | 13860-38-3 | ||||||||||||
Formula | C10H14N2O6 | ||||||||||||
Molar Mass | 258.23 | ||||||||||||
Appearance | Solid | ||||||||||||
Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
Storage |
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Reference | [1]. Svitkin YV, et al. N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Res. 2017 Jun 2;45(10):6023-6036. [2]. Andries O, et al. N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J Control Release. 2015 Nov 10;217:337-44. [3]. Nance KD, Meier JL. Modifications in an Emergency: The Role of N1-Methylpseudouridine in COVID-19 Vaccines. ACS Cent Sci. 2021;7(5):748-756. |