GEOTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325326GEOGSEfalseCodon-dependent regulation of mRNA translation and stability by ZC3H7A and ZC3H7B RNA-binding proteinsThe reduced translation elongation rate caused by the presence of non-optimal codons can negatively impact mRNA stability through translation-dependent decay. A key aspect of this process is the coupling of sensing the mRNA codon usage with the regulation of translation efficiency and stability. We found that two paralog RNA-binding proteins; ZC3H7A and ZC3H7B; which have only emerged in Chordates, preferentially bind to and reduce the stability and translation of mRNAs enriched in the non-optimal codons with A/U at their wobble sites (A/U3 codons). ZC3H7A/B engage with ribosomes that lack elongation factors and induce mRNA degradation or block translation initiation through their interactions with the CCR4-NOT and the GIGYF2/4EHP translation repressor complex, respectively. Depletion of ZC3H7A and ZC3H7B or 4EHP impairs the repression of non-optimal A/U3-rich mRNAs. This study provides insights into a unique mechanism in higher eukaryotes that couples codon usage with the regulation of translation efficiency and mRNA stability.2026/05/13GSE325326GSM9600839GSM9600828GSM9600829GSM9600846GSM9600835GSM9600847GSM9600836GSM9600825GSM9600848GSM9600837GSM9600826GSM9600827GSM9600838GSM9600842GSM9600831GSM9600843GSM9600832GSM9600844GSM9600833GSM9600845GSM9600834GSM9600840GSM9600830GSM960084134284325326Homo sapiens