GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE297nnn/GSE297337/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297337GEOGSEfalseCodon-dependent regulation of mRNA translation and stability by ZC3H7A and ZC3H7B RNA-binding proteins [Ribo-seq]The 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.2026/05/13GSE297337GSM8988836GSM8988835GSM8988838GSM8988837GSM8988829GSM8988839GSM8988830GSM8988841GSM8988840GSM8988843GSM8988832GSM8988842GSM8988831GSM8988834GSM89888332030124676297337Homo sapiens