Indirect tRNA Aminoacylation Reactions

~~~Many pathogenic bacteria, like Helicobacter pylori - the infectious agent behind most cases of stomach ulcers and stomach cancer, are missing glutaminyl- and/or asparaginyl-tRNA synthetases (GlnRS and AsnRS, respectively). In these organisms, Gln-tRNA(Gln) and Asn-tRNA(Asn) are biosynthesized indirectly via a two-step mechanism. The first step relies on the relaxed tRNA specificity of a non-discriminating glutamyl- or aspartyl-tRNA synthetase (GluRS-ND and AspRS-ND, respectively), to generate the misacylated tRNAs Glu-tRNA(Gln) and Asp-tRNA(Asn), respectively. Next, a novel, glutamine-dependent amidotransferase - Glu-Adt - repairs the amino acid side chain of each misacylated tRNA to generate Gln-tRNA(Gln) and Asn-tRNA(Asn). In this way, the fidelity of tRNA aminoacyation is maintained even in the absence of GlnRS and AsnRS.

We are broadly interested in the mechanisms that these organisms use to ensure a complete set of accurately aminoacylated tRNAs, in the absence of these enzymes.

Some of the themes to individual projects in this research area include:

• Evolution of tRNA substrate specificity
• Protein:RNA interactions/recognition
• Bacterial adaptation mechanisms
• Translational Accuracy
• Design of new anti-bacterial agents

For more information on tRNA aminoacylation projects in the lab, click here.