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. 2021 Jan 5;22:14. doi: 10.1186/s13059-020-02251-5

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© The Author(s) 2021

Open AccessThis 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Codon composition predicts mRNA stability in vertebrates. a Scheme of the procedure to train a predictive model of mRNA stability. For each endogenous mRNA, the codon frequencies and the 3′UTR length are used as predictors to train a lasso regression model [28]. The scatter plot shows the point density of predicted and observed mRNA stability (test set genes n = 7576, Pearson correlation test). b Scheme of the 1 nucleotide out of frame reporters (optimal and non-optimal): two mRNAs that differ in the codon composition due to a single nucleotide deletion (G in red, highlight with green) which creates a frameshift. The encoding mCherry fluorescent protein was followed by a cis-acting hydrolase element (P2A) and then by a coding region enriched in optimal or non-optimal codons due to the frameshift. P2A causes ribosome skipping; therefore, the mCherry is not fused to the optimal or non-optimal encoded proteins. The mRNA reporter pairs were co-injected with mRNA encoding for GFP as an internal control [24]. c Fluorescence microscopy images of representative embryos at 8 h post-injection (hpi) with the indicated 1 nt out of frame reporter and GFP. Box plot displays fluorescence quantification at 8 hpi with each reporter. The mCherry fluorescence intensity was normalized to GFP intensity in each embryo (p = 0.041, paired t test). d mRNA stability predictions for 1 nucleotide out of frame reporters in fish and human cells. In all cases, the prediction for the optimal reporter is higher than that for the non-optimal (p = 0.007, binomial test)