Poor codon optimality as a signal to degrade transcripts with frameshifts

Living organisms are error-prone. Every second a single human cell produces over 100 transcripts with a substitution, frameshift or splicing error. Multiple mRNA quality control pathways exist to degrade these transcripts. Many of these pathways involve co-translational regulation of mRNA stability, such as nonsense mediated decay (NMD) and reduced stability of transcripts with suboptimal codon usage. Recent work has shown the existence of a genetic link between NMD and codon-usage mediated mRNA decay. Here we present new computational evidence that, because the codons following most frameshift errors are suboptimal, removal of mRNAs with such errors may be mediated by degradation of mRNAs with sub-optimal codons. Thus, most transcripts that contain frameshifts are subject to two modes of degradation. Author summary Frameshifting errors are common and mRNA quality control pathways, such as nonsense-mediated decay (NMD), exist to degrade these aberrant transcripts. Recent work has shown the existence of a genetic link between NMD and codon-usage mediated mRNA decay. Here we present computational evidence that these pathways are synergic for removing frameshifts.