Codon optimality is a major determinant of mRNA stability
By Vladimir Presnyak, Najwa Alhusaini, Ying-Hsin Chen, Sophie Martin, N. Morris, Nicholas Kline, S. Olson, D. Weinberg, K. Baker, Brenton R. Graveley and 1 more. Cell, 2015
982 citations recorded by the source corpus.
Messenger RNA degradation represents a critical regulated step in gene expression. While the major pathways in turnover have been identified, accounting for disparate half-lives has been elusive. We show that codon optimality is one feature that contributes greatly to mRNA stability. Genome-wide RNA decay analysis revealed that stable mRNAs are enriched in codons designated optimal, whereas unstable mRNAs contain predominately non-optimal codons. Substitution of optimal codons with synonymous, non-optimal codons results in dramatic mRNA destabilization, while the converse substitution significantly increases stability. Further, we demonstrate that codon optimality impacts ribosome translocation, connecting the processes of translation elongation and decay through codon optimality. Finally, we show that optimal codon content accounts for the similar stabilities observed in mRNAs encoding proteins with coordinated physiological function. This work demonstrates that codon optimization exists as an mechanism to finely tune levels of mRNAs, and ultimately, proteins.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/1a5b4cef4e3a86f3fab63c4d77eef167d4cede50
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Citations in the corpus
- Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery. (2019, positive): “The modification of rare codons in protein-coding sequences with synonymous frequently occurring codons, so-called codon optimization, can result in order-of-magnitude changes in expression levels.(5,6) Modification of the 50 mRNA cap can also enhance mRNA translation by inhibiting RNA decapping and”
- Codon identity regulates mRNA stability and translation efficiency during the maternal‐to‐zygotic transition (2016, positive): “Comparison of the two methods revealed consistent effects for most codons on mRNA stability observed in the reporter library (rCSI) and the endogenous mRNAs (CSC) (Figs lF and EVlG) (zebrafish, P = le-3, R = 0.4, Spearman; Xenopus, P = 3e-3, R = 0.4, Spearman).”
- The stress granule transcriptome reveals principles of mRNA accumulation in stress granules (2017, positive): “Codon Optimality: The fraction of the optimal codon for each gene was calculated using a custom script based on codon stabilization coefficients presented in a previous report (Presnyak et al., 2016).”