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bioRxiv · 10.1101/2025.11.17.688958

Neighboring codon adjacent nucleotides have a conserved influence on mRNA decay

Sorenson, R. S.·Sieburth, L. E.
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Abstract

BackgroundDegeneracy in the genetic code has been shown to play a major role in yeast mRNA stability; differences in optimality (charged tRNA supply vs demand) among synonymous codons were revealed as a determinant of mRNA decay rates. However, whether and how much this mechanism determines mRNA decay rates in plants is unsettled. Furthermore, whether factors other than charged tRNA abundance influence codon optimality remains unexplored. ResultsHere, biased codon usage in Arabidopsis correlated with mRNA decay rates. A codon-optimality model of mRNA decay rate based on codon frequencies was tested using synonymously recoded genes. mRNA decay rates of these alleles in transgenic plants was consistent with the model predictions. Arabidopsis appears to use the same mechanism for sensing low optimality codons as yeast and humans because the N-terminal sensor domain of NOT3 is conserved. However, decay rates were also affected by codon context. Neighboring codons adjacent nucleotides consistently shifted codon correlations with decay rate in Arabidopsis, which was also observed in other published datasets revealing an influence of codon sequence on translation that is independent of charged tRNA concentrations. ConclusionsCodons frequencies explained 21% of decay rate variance, suggesting codon optimality-mediated decay is one of multiple mechanisms that determine decay rates in plants. Our study also found codon context as an additional factor that affects mRNA stability and establishes a paradigm of selection among synonymous codons decoded through wobble base pairing.

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Sorenson, R. S., Sieburth, L. E.. 2025-11-18. Neighboring codon adjacent nucleotides have a conserved influence on mRNA decay. https://doi.org/10.1101/2025.11.17.688958

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