Function
mRNA capping enzyme (Mce) is a multifunctional protein with RNA triphosphatase, RNA guanylyltransferase, RNA methyltransferase and transcription factor activities. The 5' cap of mRNA is required for its stability and efficient translation. Mce activity entails the transfer of GMP from GTP to the 5'-diphosphate end of mRNA via a enzyme-(lysyl-GMP) intermediate by RNA triphosphatase and RNA guanylyltransferaseand finally the GpppRNA is converted to m7GpppRNA by RNA methyltransferase. In Vaccinia virus the active site is at Lys260 within the conserved motif KxDG in the catalytic subunit[1].
Relevance
Inhibition of Mce may provide a route for selecting therapeutic targeting of cancer cells which acquired deregulated c-Myc which is a potent driver of many human cancers[2]
Structural highlights
- ↑ Cong P, Shuman S. Mutational analysis of mRNA capping enzyme identifies amino acids involved in GTP binding, enzyme-guanylate formation, and GMP transfer to RNA. Mol Cell Biol. 1995 Nov;15(11):6222-31. doi: 10.1128/mcb.15.11.6222. PMID:7565775 doi:https://dx.doi.org/10.1128/mcb.15.11.6222
- ↑ Lombardi O, Varshney D, Phillips NM, Cowling VH. c-Myc deregulation induces mRNA capping enzyme dependency. Oncotarget. 2016 Dec 13;7(50):82273-82288. doi: 10.18632/oncotarget.12701. PMID:27756891 doi:https://dx.doi.org/10.18632/oncotarget.12701
