Transcriptional and post-transcriptional mechanisms modulate cyclopropane fatty acid synthase through small RNAs in Escherichia coli

The small RNA (sRNA) RydC strongly activates cfa, which encodes the cyclopropane fatty acid synthase. Previous work demonstrated that RydC activation of cfa increases conversion of unsaturated fatty acids to cyclopropanated fatty acids in membrane lipids and changes the biophysical properties of membranes, making cells more resistant to acid stress. The conditions and regulators that control RydC synthesis had not previously been identified. In this study, we demonstrate that RydC regulation of cfa is important for resistance to membrane-disrupting conditions. We identify a GntR-family transcription factor, YieP, that represses rydC transcription and show that YieP indirectly regulates cfa through RydC. YieP positively autoregulates its own transcription. We further identify additional sRNA regulatory inputs that contribute to control of RydC and cfa. The translation of yieP is repressed by the Fnr-dependent sRNA, FnrS, making FnrS an indirect activator of rydC and cfa. Conversely, RydC activity on cfa is antagonized by the OmpR-dependent sRNA OmrB. Altogether, this work illuminates a complex regulatory network involving transcriptional and post-transcriptional inputs that link control of membrane biophysical properties to multiple environmental signals. ImportanceBacteria experience many environmental stresses that challenge their membrane integrity. To withstand these challenges, bacteria sense what stress is occurring and mount a response that protects membranes. Previous work documented the important roles of small RNA (sRNA) regulators in membrane stress responses. One sRNA, RydC, helps cells cope with membrane-disrupting stresses by promoting changes in the types of lipids incorporated into membranes. In this study, we identified a regulator, YieP, that controls when RydC is produced, and additional sRNA regulators that modulate YieP levels and RydC activity. These findings illuminate a complex regulatory network that helps bacteria sense and respond to membrane stress.