The Eukaryotic mRNA Cap Structure

Abstract

In contrast to bacteria, eukaryotic cellular cytoplasmic (except for organellar) mRNAs are blocked at their 5′ ends by a unique structure – the m 7 GpppN cap, where N is any nucleotide and m is a methyl group. The cap is an essential mRNA feature as it is critical to several steps of gene expression. Its role in translation and mRNA stability is particularly well studied. Interest in the cap has recently surged given the development of mRNA‐based vaccines and mRNA therapeutics. Key Concepts The m 7 GpppN cap plays a pivotal role in gene expression in eukaryotes. The rapid development of SARS‐CoV‐2 mRNA vaccines underscores the importance of funding fundamental research, without a translational milestone, as this is the path that often leads to paradigm shifts in knowledge base. Many forms of translation control (stimulation and repression) are mediated by different cap‐binding proteins and underscore the broad roles that the cap plays in gene expression. Development of synthetic cap structures enables the implementation of user‐defined regulation of gene expression. Fundamental research on the cap structure over the last 45 years has set the stage for its use in RNA‐based medicines (e.g. SARS‐CoV‐2 mRNA vaccines) that could be rapidly deployed with guaranteed performance in vivo .