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A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity.

Authors
  • Scopino, Kristen1
  • Williams, Elliot1, 2
  • Elsayed, Abdelrahman1, 2
  • Barr, William A1
  • Krizanc, Daniel2, 3
  • Thayer, Kelly M2, 3, 4
  • Weir, Michael P1, 3
  • 1 Department of Biology, Wesleyan University, Middletown, CT 06459, USA.
  • 2 Department of Mathematics and Computer Science, Wesleyan University, Middletown, CT 06459, USA.
  • 3 College of Integrative Sciences, Wesleyan University, Middletown, CT 06459, USA.
  • 4 Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA.
Type
Published Article
Journal
Biomolecules
Publisher
MDPI AG
Publication Date
Jun 03, 2020
Volume
10
Issue
6
Identifiers
DOI: 10.3390/biom10060849
PMID: 32503152
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A longstanding challenge is to understand how ribosomes parse mRNA open reading frames (ORFs). Significantly, GCN codons are over-represented in the 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 the 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 observed 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 the GCN-mediated regulation of protein translation.

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