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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7357141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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