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bioRxiv · 10.1101/2020.04.28.058271

A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity

Scopino, K.·Williams, E.·Elsayed, A.·Barr, W. A.·Krizanc, D.·Thayer, K. M.·Weir, M. P.
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Abstract

GCN codons are over-represented in initial codons of ORFs of prokaryote and eukaryote mRNAs. We describe a ribosome rRNA-protein surface that interacts with an mRNA GCN codon when next-in-line for the ribosome A site. The interaction surface is comprised of the edges of two stacked rRNA bases: the Watson-Crick edge of 16S/18S rRNA C1054 and adjacent Hoogsteen edge of A1196 (Escherichia coli 16S rRNA numbering). Also part of the interaction surface, the planar guanidinium group of a conserved Arginine (R146 of yeast ribosomal protein Rps3) is stacked adjacent to A1196. On its other side, the interaction surface is anchored to the ribosome A site through base stacking of C1054 with the wobble anticodon base of the A-site tRNA. Using Molecular Dynamics simulations of a 495-residue subsystem of translocating ribosomes, we observe base pairing of C1054 to nucleotide G at position 1 of the next-in-line codon, consistent with previous cryo-EM observations, and hydrogen bonding of A1196 and R146 to C at position 2. Hydrogen bonding to both of these codon positions is significantly weakened when C at position 2 is changed to G, A or U. These sequence-sensitive mRNA-ribosome interactions at the C1054-A1196-R146 (CAR) surface potentially contribute to GCN-mediated regulation of protein translation.

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Scopino, K., Williams, E., Elsayed, A., Barr, W. A., Krizanc, D., Thayer, K. M., Weir, M. P.. 2020-04-29. A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity. https://doi.org/10.1101/2020.04.28.058271

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