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iCodon customizes gene expression based on the codon composition
Messenger RNA (mRNA) stability substantially impacts steady-state gene expression levels in a cell. mRNA stability is strongly affected by codon composition in a translation-dependent manner across species, through a mechanism termed codon optimality. We have developed iCodon (www.iCodon.org), an al...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287306/ https://www.ncbi.nlm.nih.gov/pubmed/35840631 http://dx.doi.org/10.1038/s41598-022-15526-7 |
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author | Diez, Michay Medina-Muñoz, Santiago Gerardo Castellano, Luciana Andrea da Silva Pescador, Gabriel Wu, Qiushuang Bazzini, Ariel Alejandro |
author_facet | Diez, Michay Medina-Muñoz, Santiago Gerardo Castellano, Luciana Andrea da Silva Pescador, Gabriel Wu, Qiushuang Bazzini, Ariel Alejandro |
author_sort | Diez, Michay |
collection | PubMed |
description | Messenger RNA (mRNA) stability substantially impacts steady-state gene expression levels in a cell. mRNA stability is strongly affected by codon composition in a translation-dependent manner across species, through a mechanism termed codon optimality. We have developed iCodon (www.iCodon.org), an algorithm for customizing mRNA expression through the introduction of synonymous codon substitutions into the coding sequence. iCodon is optimized for four vertebrate transcriptomes: mouse, human, frog, and fish. Users can predict the mRNA stability of any coding sequence based on its codon composition and subsequently generate more stable (optimized) or unstable (deoptimized) variants encoding for the same protein. Further, we show that codon optimality predictions correlate with both mRNA stability using a massive reporter library and expression levels using fluorescent reporters and analysis of endogenous gene expression in zebrafish embryos and/or human cells. Therefore, iCodon will benefit basic biological research, as well as a wide range of applications for biotechnology and biomedicine. |
format | Online Article Text |
id | pubmed-9287306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92873062022-07-17 iCodon customizes gene expression based on the codon composition Diez, Michay Medina-Muñoz, Santiago Gerardo Castellano, Luciana Andrea da Silva Pescador, Gabriel Wu, Qiushuang Bazzini, Ariel Alejandro Sci Rep Article Messenger RNA (mRNA) stability substantially impacts steady-state gene expression levels in a cell. mRNA stability is strongly affected by codon composition in a translation-dependent manner across species, through a mechanism termed codon optimality. We have developed iCodon (www.iCodon.org), an algorithm for customizing mRNA expression through the introduction of synonymous codon substitutions into the coding sequence. iCodon is optimized for four vertebrate transcriptomes: mouse, human, frog, and fish. Users can predict the mRNA stability of any coding sequence based on its codon composition and subsequently generate more stable (optimized) or unstable (deoptimized) variants encoding for the same protein. Further, we show that codon optimality predictions correlate with both mRNA stability using a massive reporter library and expression levels using fluorescent reporters and analysis of endogenous gene expression in zebrafish embryos and/or human cells. Therefore, iCodon will benefit basic biological research, as well as a wide range of applications for biotechnology and biomedicine. Nature Publishing Group UK 2022-07-15 /pmc/articles/PMC9287306/ /pubmed/35840631 http://dx.doi.org/10.1038/s41598-022-15526-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Diez, Michay Medina-Muñoz, Santiago Gerardo Castellano, Luciana Andrea da Silva Pescador, Gabriel Wu, Qiushuang Bazzini, Ariel Alejandro iCodon customizes gene expression based on the codon composition |
title | iCodon customizes gene expression based on the codon composition |
title_full | iCodon customizes gene expression based on the codon composition |
title_fullStr | iCodon customizes gene expression based on the codon composition |
title_full_unstemmed | iCodon customizes gene expression based on the codon composition |
title_short | iCodon customizes gene expression based on the codon composition |
title_sort | icodon customizes gene expression based on the codon composition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287306/ https://www.ncbi.nlm.nih.gov/pubmed/35840631 http://dx.doi.org/10.1038/s41598-022-15526-7 |
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