iCodon customizes gene expression based on the codon composition.

Autor: Diez M; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO, 64110, USA., Medina-Muñoz SG; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO, 64110, USA.; National Laboratory of Genomics for Biodiversity (LANGEBIO), Unit of Advanced Genomics, 36824, Irapuato, Mexico., Castellano LA; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO, 64110, USA., da Silva Pescador G; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO, 64110, USA., Wu Q; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO, 64110, USA., Bazzini AA; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO, 64110, USA. arb@stowers.org.; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA. arb@stowers.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jul 15; Vol. 12 (1), pp. 12126. Date of Electronic Publication: 2022 Jul 15.
DOI: 10.1038/s41598-022-15526-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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