Switching fatty acid metabolism by an RNA-controlled feed forward loop.

Hfq (host factor for phage Q beta) is key for posttranscriptional gene regulation in many bacteria. Hfq's function is to stabilize sRNAs and to facilitate base-pairing with -encoded target mRNAs. Loss of Hfq typically results in pleiotropic phenotypes, and, in the major human pathogen , Hfq inactivation has been linked to reduced virulence, failure to produce biofilms, and impaired intercellular communication. However, the RNA ligands of Hfq in are currently unknown. Here, we used RIP-seq (RNA immunoprecipitation followed by high-throughput sequencing) analysis to identify Hfq-bound RNAs in Our work revealed 603 coding and 85 noncoding transcripts associated with Hfq, including 44 sRNAs originating from the 3' end of mRNAs. Detailed investigation of one of these latter transcripts, named FarS (fatty acid regulated sRNA), showed that this sRNA is produced by RNase E-mediated maturation of the 3'UTR, and, together with Hfq, inhibits the expression of two paralogous mRNAs. The and genes are antagonistically regulated by the major fatty acid transcription factor, FadR, and we show that, together, FadR, FarS, and FadE constitute a mixed feed-forward loop regulating the transition between fatty acid biosynthesis and degradation in Our results provide the molecular basis for studies on Hfq in and highlight the importance of a previously unrecognized sRNA for fatty acid metabolism in this major human pathogen.