An evolutionarily conserved RNA stem-loop functions as a sensor that directs feedback regulation of RNase E gene expression

RNase E is a key regulatory enzyme that controls the principal pathway for mRNA degradation in Escherichia coli. The cellular concentration of this endonuclease is governed by a feedback mechanism in which RNase E tightly regulates its own synthesis. Autoregulation is mediated in cis by the 361-nucleotide 5' untranslated region (UTR) of me (RNase E) mRNA. Here we report the determination of the secondary structure of the me 5' UTR by phylogenetic comparison and chemical alkylation, together with dissection studies to identify the 5' UTR element that mediates autoregulation. Our findings reveal that the structure and function of the me 5' UTRs are evolutionarily well conserved despite extensive sequence divergence. Within the me 5' UTRs are multiple RNA secondary structure elements, two of which function in cis to mediate feedback regulation of me gene expression. The more potent of these two elements is a stem-loop structure containing an internal loop whose sequence is the most highly conserved of any region of the me 5' UTR. Our data show that this stem-loop functions as a sensor of cellular RNase E activity that directs autoregulation by modulating the degradation rate of me mRNA in response to changes in RNase E activity.