Codon optimality is a major determinant of mRNA stability

Vladimir Presnyak, Najwa Alhusaini, Ying Hsin Chen, Sophie Martin, Nathan Morris, Nicholas Kline, Sara Olson, David Weinberg, Kristian E. Baker, Brenton R. Graveley, Jeff Coller

Research output: Contribution to journalArticlepeer-review

Abstract

mRNA degradation represents a critical regulated step in gene expression. Although 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, whereas 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 a mechanism to finely tune levels of mRNAs and, ultimately, proteins.

Original languageEnglish (US)
Pages (from-to)1111-1124
Number of pages14
JournalCell
Volume160
Issue number6
DOIs
StatePublished - Mar 15 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Codon optimality is a major determinant of mRNA stability'. Together they form a unique fingerprint.

Cite this