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A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity

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 i...

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Autores principales: Scopino, Kristen, Williams, Elliot, Elsayed, Abdelrahman, Barr, William A., Krizanc, Daniel, Thayer, Kelly M., Weir, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357141/
https://www.ncbi.nlm.nih.gov/pubmed/32503152
http://dx.doi.org/10.3390/biom10060849
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author Scopino, Kristen
Williams, Elliot
Elsayed, Abdelrahman
Barr, William A.
Krizanc, Daniel
Thayer, Kelly M.
Weir, Michael P.
author_facet Scopino, Kristen
Williams, Elliot
Elsayed, Abdelrahman
Barr, William A.
Krizanc, Daniel
Thayer, Kelly M.
Weir, Michael P.
author_sort Scopino, Kristen
collection PubMed
description 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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spelling pubmed-73571412020-07-23 A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity Scopino, Kristen Williams, Elliot Elsayed, Abdelrahman Barr, William A. Krizanc, Daniel Thayer, Kelly M. Weir, Michael P. Biomolecules Article 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. MDPI 2020-06-03 /pmc/articles/PMC7357141/ /pubmed/32503152 http://dx.doi.org/10.3390/biom10060849 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scopino, Kristen
Williams, Elliot
Elsayed, Abdelrahman
Barr, William A.
Krizanc, Daniel
Thayer, Kelly M.
Weir, Michael P.
A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity
title A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity
title_full A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity
title_fullStr A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity
title_full_unstemmed A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity
title_short A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity
title_sort ribosome interaction surface sensitive to mrna gcn periodicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357141/
https://www.ncbi.nlm.nih.gov/pubmed/32503152
http://dx.doi.org/10.3390/biom10060849
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