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bioRxiv · 10.1101/2022.01.06.475228

The CAR mRNA-Interaction Surface is a Zipper Extension of the Ribosome A Site

Dalgarno, C.·Scopino, K.·Raval, M.·Nachmanoff, C.·Sakkas, E.·Krizanc, D.·Thayer, K.·Weir, M. P.
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Abstract

The ribosome CAR interaction surface behaves like an extension of the decoding center A site and has H-bond interactions with the +1 codon that is next in line to enter the A site. Through molecular dynamics simulations, we investigated the codon sequence specificity of this CAR-mRNA interaction and discovered a strong preference for GCN codons, suggesting that there may be a sequence-dependent layer of translational regulation dependent on the CAR interaction surface. Dissection of the CAR-mRNA interaction through nucleotide substitution experiments showed that the first nucleotide of the +1 codon dominates over the second nucleotide position, consistent with an energetically favorable zipper-like activity that emanates from the A site through the CAR-mRNA interface. The +1 codon/CAR interaction is also affected by the identity of nucleotide 3 of +1 GCN codons which influences the stacking of G and C. Clustering analysis suggests that the A site decoding center adopts different neighborhood substates that depend on the identity of the +1 codon.

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Dalgarno, C., Scopino, K., Raval, M., Nachmanoff, C., Sakkas, E., Krizanc, D., Thayer, K., Weir, M. P.. 2022-01-06. The CAR mRNA-Interaction Surface is a Zipper Extension of the Ribosome A Site. https://doi.org/10.1101/2022.01.06.475228

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