ICodon Customizes Gene Expression Based on the Codon Composition

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jul 15

PMID 35840631

Authors

Michay Diez

Santiago Gerardo Medina-Munoz

Luciana Andrea Castellano

Gabriel da Silva Pescador

Qiushuang Wu

Ariel Alejandro Bazzini

Affiliations

Soon will be listed here.

Abstract

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.

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