Neighboring codon adjacent nucleotides have a conserved influence on mRNA decay

Area of Science:

• Molecular Biology
• Genetics
• Plant Science

Background:

• Genetic code degeneracy impacts mRNA stability in yeast.
• Codon optimality, defined by tRNA supply and demand, affects mRNA decay rates.
• The role of this mechanism in plants and other factors influencing codon optimality were unexplored.

Purpose of the Study:

• To investigate whether codon optimality influences mRNA decay rates in plants.
• To explore factors beyond charged tRNA abundance that affect codon optimality.
• To determine the extent to which codon usage impacts mRNA stability in Arabidopsis.

Main Methods:

• Correlating biased codon usage with mRNA decay rates in Arabidopsis.
• Testing a codon-optimality model using synonymously recoded genes.
• Analyzing mRNA decay rates in transgenic plants and comparing with model predictions.
• Investigating the influence of codon context on mRNA decay.

Main Results:

• Biased codon usage in Arabidopsis correlated with mRNA decay rates.
• A codon-optimality model accurately predicted mRNA decay rates for recoded genes.
• The NOT3 gene's conserved sensor domain suggests a conserved mechanism for sensing suboptimal codons.
• Codon context, specifically adjacent nucleotides, influenced mRNA decay rates independently of tRNA levels.

Conclusions:

• Codon frequencies explain 21% of mRNA decay rate variance in plants.
• Codon optimality-mediated decay is one of several mechanisms regulating plant mRNA stability.
• Codon context is an additional factor affecting mRNA stability.
• A paradigm of selection among synonymous codons decoded via wobble base pairing is established.