Wybutosine

A hypermodified nucleoside found in tRNA

Wybutosine (abbreviated as yW) is a hypermodified nucleoside found in the tRNA of eukaryotic organisms. It is specifically located at position 37, adjacent to the anticodon, in phenylalanine tRNA (tRNA^Phe). Wybutosine is known for its role in stabilizing codon-anticodon interactions during translation, thereby enhancing the accuracy and efficiency of protein synthesis.

Structure and Biosynthesis

Wybutosine is derived from the nucleoside guanosine through a series of complex enzymatic modifications. The biosynthesis of wybutosine involves multiple steps:

1. Methylation of Guanosine: The initial step involves the methylation of guanosine at the N7 position, catalyzed by the enzyme TRMT12. 2. Addition of a Methoxycarbonyl Group: The next step involves the addition of a methoxycarbonyl group at the C2 position, facilitated by the enzyme TYW1. 3. Formation of the Tricyclic Core: The tricyclic core of wybutosine is formed through the action of the enzyme TYW2, which catalyzes the cyclization of the intermediate. 4. Further Modifications: Additional modifications, including methylation and hydroxylation, are carried out by enzymes such as TYW3 and TYW4, leading to the mature wybutosine structure.

Function

Wybutosine plays a critical role in maintaining the fidelity of protein synthesis. By stabilizing the codon-anticodon interaction, it prevents frameshifting and ensures that the correct amino acids are incorporated into the growing polypeptide chain. This is particularly important in the context of the ribosome, where precise base pairing is crucial for accurate translation.

Clinical Significance

Alterations in wybutosine biosynthesis have been linked to various human diseases. Defects in the enzymes responsible for wybutosine modification can lead to translational errors, which may contribute to the development of certain genetic disorders. Research is ongoing to explore the potential therapeutic implications of targeting wybutosine biosynthesis pathways.

Research and Applications

Wybutosine and its biosynthetic pathway are subjects of extensive research due to their implications in molecular biology and genetics. Understanding the role of wybutosine in translation can provide insights into the mechanisms of gene expression regulation and the evolution of the genetic code.

Also see

• Transfer RNA
• Translation (biology)
• Nucleoside modifications in RNA
• Ribosome
• Protein synthesis