guanylyltransferases

Guanylyltransferases are enzymes that catalyze the transfer of a guanylyl group from guanosine triphosphate (GTP) to an acceptor molecule. The best-known example occurs in RNA capping, where these enzymes add GMP to the 5' end of a nascent RNA that bears a 5'-diphosphate, forming a 5'-5' triphosphate linkage known as the cap (GpppN). The cap is later modified by methyltransferases to a mature methylated cap that supports downstream processes.

Mechanistically, many guanylyltransferases operate via a covalent enzyme–GMP intermediate. After an RNA 5' triphosphatase removes the gamma phosphate from the nascent transcript, the guanylyltransferase uses GTP to generate the enzyme–GMP intermediate and then transfers GMP to the RNA end, releasing pyrophosphate. The resulting cap structure can be further methylated to form the commonly encountered m7G cap, which is recognized by cap-binding proteins and translation initiation factors.

Guanylyltransferases vary in their organization. In yeast, Cet1p provides the guanylyltransferase activity while Ceg1p partners as a subunit; in humans RNGTT is a bifunctional enzyme with both triphosphatase and guanylyltransferase activities; in many poxviruses, capping functions are carried by separate viral proteins. Some guanylyltransferases act on noncanonical substrates in specialized biological pathways.

Biological significance is substantial: the cap structure stabilizes mRNA, facilitates splicing and nuclear export, and promotes efficient translation initiation. Because several viruses encode their own capping enzymes, guanylyltransferases are of interest for antiviral research and for understanding diverse RNA-processing strategies.