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Translation initiation events on structured eukaryotic mRNAs generate gene expression noise

Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to...

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Autores principales: Dacheux, Estelle, Malys, Naglis, Meng, Xiang, Ramachandran, Vinoy, Mendes, Pedro, McCarthy, John EG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499741/
https://www.ncbi.nlm.nih.gov/pubmed/28521011
http://dx.doi.org/10.1093/nar/gkx430
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author Dacheux, Estelle
Malys, Naglis
Meng, Xiang
Ramachandran, Vinoy
Mendes, Pedro
McCarthy, John EG
author_facet Dacheux, Estelle
Malys, Naglis
Meng, Xiang
Ramachandran, Vinoy
Mendes, Pedro
McCarthy, John EG
author_sort Dacheux, Estelle
collection PubMed
description Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem–loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise. The noise-enhancing effect of the stem–loop structure also remains operational when combined with an upstream open reading frame. This has broad significance, since these elements are known to modulate the expression of a diversity of eukaryotic genes. Our findings suggest a mechanism for posttranscriptional noise generation that will contribute to understanding of the generally poor correlation between protein-level stochasticity and transcriptional bursting. We propose that posttranscriptional stochasticity can be linked to cycles of folding/unfolding of a stem–loop structure, or to interconversion between higher-order structural conformations of a G-rich motif, and have created a correspondingly configured computational model that generates fits to the experimental data. Stochastic events occurring during the ribosomal scanning process can therefore feature alongside transcriptional bursting as a source of noise.
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spelling pubmed-54997412017-07-10 Translation initiation events on structured eukaryotic mRNAs generate gene expression noise Dacheux, Estelle Malys, Naglis Meng, Xiang Ramachandran, Vinoy Mendes, Pedro McCarthy, John EG Nucleic Acids Res Synthetic Biology and Bioengineering Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem–loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise. The noise-enhancing effect of the stem–loop structure also remains operational when combined with an upstream open reading frame. This has broad significance, since these elements are known to modulate the expression of a diversity of eukaryotic genes. Our findings suggest a mechanism for posttranscriptional noise generation that will contribute to understanding of the generally poor correlation between protein-level stochasticity and transcriptional bursting. We propose that posttranscriptional stochasticity can be linked to cycles of folding/unfolding of a stem–loop structure, or to interconversion between higher-order structural conformations of a G-rich motif, and have created a correspondingly configured computational model that generates fits to the experimental data. Stochastic events occurring during the ribosomal scanning process can therefore feature alongside transcriptional bursting as a source of noise. Oxford University Press 2017-06-20 2017-05-17 /pmc/articles/PMC5499741/ /pubmed/28521011 http://dx.doi.org/10.1093/nar/gkx430 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Synthetic Biology and Bioengineering
Dacheux, Estelle
Malys, Naglis
Meng, Xiang
Ramachandran, Vinoy
Mendes, Pedro
McCarthy, John EG
Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
title Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
title_full Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
title_fullStr Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
title_full_unstemmed Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
title_short Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
title_sort translation initiation events on structured eukaryotic mrnas generate gene expression noise
topic Synthetic Biology and Bioengineering
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499741/
https://www.ncbi.nlm.nih.gov/pubmed/28521011
http://dx.doi.org/10.1093/nar/gkx430
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