Global regulation by CsrA and its RNA antagonists

The sequence-specific RNA binding protein CsrAis employed by diverse bacteria in the posttranscriptionalregulation of gene expression. Its binding interactions with RNAhave been documented at atomic resolution and shown to alterRNA secondary structure, RNA stability, translation, and/orRho-mediated transcription termination through a growingnumber of molecular mechanisms. In Gammaproteobacteria,small regulatory RNAs (sRNAs) that contain multiple CsrAbinding sites compete with mRNA for binding to CsrA, therebysequestering and antagonizing this protein. Both the synthesisand turnover of these sRNAs are regulated, allowing CsrA activityto be rapidly and efficiently adjusted in response to nutritionalconditions and stresses. Feedback loops between the Csrregulatory components improve the dynamics of signalresponse by the Csr system. The Csr system of Escherichia coli isintimately interconnected with other global regulatory systems,permitting it to contribute to regulation by those systems.In some species, a protein antagonist of CsrA functions as partof a checkpoint for flagellum biosynthesis. In other species,a protein antagonist participates in a mechanism in which a typeIII secretion system is used for sensing interactions with hostcells. Recent transcriptomics studies reveal vast effects of CsrAon gene expression through direct binding to hundreds ofmRNAs, and indirectly through its effects on the expression ofdozens of transcription factors. CsrA binding to base-pairingsRNAs and novel mRNA segments, such as the 3' untranslatedregion and deep within coding regions, predict its participationin yet-to-be-discovered regulatory mechanisms.