Ribosome-mRNA Interactions During Protein Synthesis
We are interested in ribosome function during protein translation. GNN codons are over-represented in codons of protein Open Reading Frames (ORFs). This GNN periodicity is particularly pronounced in genes with high protein expression. We speculate that the GNN periodicity may reflect mRNA-ribosome interactions that occur when the mRNA is threaded through the ribosome during translocation. We are exploring this hypothesis using a combination of molecular genetics and Molecular Dynamics computational approaches.
Using a subsystem of the ribosome, including the neighborhood of the decoding center where the A-site mRNA codon base pairs with the tRNA anticodon, we have discovered an interaction surface that hydrogen-bonds to the +1 codon next in line to enter the A site. At the beginning of translocation, the interaction surface is positioned immediately adjacent to the tRNA anticodon, aligning it with the +1 codon in the mRNA. The interaction surface consists of the edges of two stacked rRNA bases—the Watson-Crick edge of 16S/18S C1054 and the Hoogsteen edge of A1196 (E. coli 16S rRNA numbering)—and the guanidinium group of R146 of yeast ribosomal protein Rps3 which pi-stacks with A1196. This C1054-A1196-R146 (CAR) surface H-bonds to the first two nucleotides of the +1 codon 
and this interaction is particularly strong when the codon starts with a G nucleotide (GNN). We are currently exploring the sequence dependence of this mRNA-CAR interaction which potentially contributes to GNN-mediated regulation of protein translation.
We have undergraduate and graduate research opportunities in our Biology Department and Molecular Biophysics Program.
Funding: National Institutes of Health
Figure: CAR interaction surface