The control of mammalian mRNA turnover and translation has been linked almost exclusively to specific cis-elements within the 5'- and 3'-untranslated regions (UTRs) of the mature mRNA. However, instances of regulated turnover and translation via cis-elements within the coding region (CR) of mRNAs are accumulating. Here, we describe the regulation of post-transcriptional fate through trans-binding factors (RNA-binding proteins and microRNAs) that function via CR sequences. We discuss how the CR enriches the post-transcriptional control of gene expression, and predict that new high-throughput technologies will enable a more mainstream study of CR-governed gene regulation.