Polysome propensity and tunable thresholds in coding sequence length enable differential mRNA stability

The half-life of mRNAs, as well as their translation, increases proportionally to the optimal codons, indicating a tight coupling of codon-dependent differential translation and degradation. Little is known about the regulation of this coupling. We found that the coupling in yeast displays a dichotomous behavior regarding the mRNA coding sequence length. Below a critical length, codon optimality fails to affect the stability of mRNAs even though they can be efficiently translated into short peptides and proteins. Above this threshold length, codon optimality-dependent differential mRNA stability emerges in a switch-like fashion, which coincides with a similar increase in the polysome propensity of the mRNAs. This threshold length can be tuned by the untranslated regions (UTR). Some of these UTRs can destabilize mRNAs without reducing translation, which plays a role in controlling the amplitude of the oscillatory expression of cell-cycle genes. Our findings help understand the translation of short peptides from noncoding RNAs and the translation by localized monosomes in neurons. Overall design: To investigate the translational status of transcripts, with respect to the number of ribosomes associated with them, we carried out polysome profiling of yeast BY4743 isogenic strains and carried out RNASeq of each of the fractions with them corresponding to specific number of ribosomes.