mRNA-capping enzyme (CE) (CE)

The mRNA capping machinery, primarily centered on the mRNA-capping enzyme (CE), is a vital protein complex responsible for the post-transcriptional modification of the 5' end of nascent mRNA transcripts. This multi-step process involves three sequential enzymatic reactions: the removal of the gamma-phosphate from the 5' triphosphate end (triphosphatase), the addition of a GMP molecule (guanylyltransferase), and the methylation of the terminal guanine (methyltransferase) [4, 5]. In eukaryotes, this modification is essential for protecting mRNA from exonuclease degradation, facilitating nuclear export, and initiating protein translation by recruiting initiation factors like eIF4E [1, 15]. Furthermore, the formation of a Cap-1 structure through 2'-O-methylation allows the cell to distinguish its own RNA from foreign viral RNA, effectively evading the host's innate immune system [10, 11]. Because many viruses encode their own distinct capping enzymes to ensure the stability and translation of their viral genomes, these enzymes serve as critical targets for antiviral drug development, including treatments for SARS-CoV-2 and Influenza [2, 14]. Targeting these specific viral mechanisms allows for the inhibition of viral replication while potentially restoring the host's ability to mount an immune response against uncapped viral transcripts [9, 12].

Other names

mRNA capping complexRNA-capping enzymeRNGTTRNMTHuman capping enzyme (HCE)5' capping machineryGuanine-N7-methyltransferaseRNA guanylyltransferase

Inhibition of RNA triphosphatase activity; inhibition of RNA guanylyltransferase activity; inhibition of Guanine-N7-methyltransferase (N7-MTase) activity; inhibition of 2'-O-methyltransferase (2'O-MTase) activity; competitive inhibition of S-adenosylmethionine (SAM) binding; competitive inhibition of GTP binding