The identity and methylation status of the first transcribed nucleotide in eukaryotic mRNA 5′ cap modulates protein expression in living cells

Pawel J. Sikorski, Marcin Warminski, Dorota Kubacka, Tomasz Ratajczak, Dominika Nowis, Joanna Kowalska, and Jacek Jemielity

Nucleic Acids Res (2020) 48(4): 1607– 1626, doi:10.1093/nar/gkaa032

Using in vitro generated capped mRNA, the influence of the first transcribed nucleotide and its methylation status on translation was systematically studied. Translation rates were found to depend strongly on the identity of the nucleotide and its methylation, mRNA purity and the immune state of the cell. These findings are of broad interest both in terms of describing potential strategies to improve expression of exogenous proteins (for applications such as gene therapies) while also providing considerable new insights in the mechanisms of regulation of mRNA translation.

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