Guanylyltransferase

Guanylyltransferase is an enzyme that plays a crucial role in the process of mRNA capping, which is essential for mRNA stability and translation. This enzyme catalyzes the transfer of a guanylyl group from GTP to the 5' end of the mRNA, forming a 5'-5' triphosphate link. The capped mRNA is then recognized by various proteins involved in RNA splicing, nuclear export, and translation initiation.

Function

Guanylyltransferase activity is critical for the creation of the cap structure found at the 5' end of all eukaryotic mRNAs. This cap, known as cap-0, consists of a 7-methylguanosine residue linked to the first nucleotide of the mRNA via a unique 5'-5' triphosphate bridge. The cap structure protects mRNA from degradation by exonucleases, aids in the export of mRNA from the nucleus, and is involved in the initiation of translation by facilitating the binding of the mRNA to the ribosome.

Mechanism

The mechanism of action of guanylyltransferase involves two main steps. First, the enzyme binds to GTP and cleaves the pyrophosphate bond, leaving a guanylyl-enzyme intermediate. Next, this intermediate reacts with the 5' triphosphate end of the mRNA, transferring the guanyl group to form the cap structure. This reaction is highly specific and efficient, ensuring that mRNA molecules are properly capped before they are exported to the cytoplasm.

Clinical Significance

Alterations in the mRNA capping process, including the function of guanylyltransferase, can lead to various diseases and disorders. For example, defects in mRNA capping enzymes have been linked to congenital diseases and are being explored as potential targets for antiviral and anticancer therapies. Inhibitors of guanylyltransferase are considered potential antiviral agents because many viruses rely on host cell capping mechanisms to stabilize their own mRNA.

See Also

• RNA polymerase
• 5' cap
• mRNA surveillance
• Nucleotide
• Translation