Extensive reshaping of bacterial operons by programmed mRNA decay

Bacterial operons synchronize the expression of multiple genes by placing them under the control of a shared promoter. It was previously shown that polycistronic transcripts can undergo differential RNA decay, leaving some genes within the polycistron more stable than others, but the extent of regulation by differential mRNA decay or its evolutionary conservation remains unknown. Here, we find that a substantial fraction of E. coli genes display non-uniform mRNA stoichiometries despite being coded from the same operon. We further show that these altered operon stoichiometries are shaped post-transcriptionally by differential mRNA decay, which is regulated by RNA structures that protect specific regions in the transcript from degradation. These protective RNA structures are generally coded within the protein-coding regions of the regulated genes and are frequently evolutionarily conserved. Furthermore, we provide evidence that differences in ribosome densities across polycistronic transcript segments, together with the conserved structural RNA elements, play a major role in the differential decay process. Our results highlight a major role for differential mRNA decay in shaping bacterial transcriptomes.