The mechanics of mRNA capping enzymes

The core Cap-0 structure of eukaryotes contains a N7-methylguanosine connected to the 5′ nucleotide of messenger RNA molecule via a 5′-5′ triphosphate linkage (m7GpppN-). In nature, RNA capping enzymes bind to the mRNA-transcribing RNA polymerase (such as RNA polymerase II in mammalian cells) and install the Cap-0 structure to the 5′ end of the transcribing mRNA in three enzymatic steps. Our lab focuses on RNA capping enzymes from large DNA viruses, such as Vaccinia virus and Faustovirus. These RNA capping enzymes contain all three catalytic activities on distinct structural domains.

Model of a molecular structure with TPase subunit in blue, GTase subunit in orange and  N7MTase subunit in green

 

Our research focuses on mechanistic properties that help coordinate the three enzyme activities and make these sophisticated enzymes highly efficient.

Flow diagram and graphs showing RNA species over time with three enzyme activities (TPase, GTase, N7-MTase)

 

References:
Ramanathan et al (2016), Nucl. Acids Res.PMID 27317694
Chan et al (2023), RNAPMID 37625853