CsrA enters Hfq's territory: Regulation of a base‐pairing small RNA

• Published in: Molecular microbiology 2022-01, Vol.117 (1), p.4-9
• Main Authors: Stenum, Thomas Søndergaard, Holmqvist, Erik
• Format: Article
• Language: English
• Subjects: Base Pairing; Binding; CsrA; Hfq; Host Factor 1 Protein - genetics; Identification methods; Microbiology; post-transcriptional regulation; Proteins; RBP; Regulation; Ribonuclease E; RNA, Bacterial - metabolism; RNA, Messenger - metabolism; RNA, Small Untranslated - genetics; RNA-binding protein; RNase E; Sequestering; spot 42; Transcription
• ISSN: 0950-382X; 1365-2958; 1365-2958
• DOI: 10.1111/mmi.14785

Post‐transcriptional regulatory networks in Gammaproteobacteria are to a large extent built around the two globally acting RNA‐binding proteins (RBPs) CsrA and Hfq. Both RBPs interact with small regulatory RNAs (sRNAs), but the functional outcomes of these interactions are generally distinct. Whereas Hfq both stabilizes sRNAs and promotes their base‐pairing to target mRNAs, the sRNAs bound by CsrA act as sequestering molecules that titrate the RBP away from its mRNA targets. In this issue of Molecular Microbiology, Lai et al. reveal that CsrA interacts with the Hfq‐associated and base‐pairing sRNA Spot 42. In this case, CsrA increases Spot 42 stability by masking a cleavage site for endoribonuclease RNase E, thereby promoting Spot 42‐dependent regulation of srlA mRNA. Interestingly, the effect of CsrA on srlA expression is two‐fold. In addition to affecting Spot 42‐dependent regulation, CsrA directly inhibits translation of SrlM, an activator of srlA transcription. Together, this study reveals a new function for CsrA and indicates more intricate connections between the CsrA and Hfq networks than previously anticipated. Several recent studies have identified additional RBPs that interact with sRNAs. With new RBP identification methods at hand, it will be intriguing to see how many more sRNA‐binding proteins will be uncovered. The RNA‐binding proteins CsrA and Hfq are key post‐transcriptional regulators in many bacterial species. This commentary discusses the regulatory connections between CsrA and Hfq in the light of a new study by Lai et al., published in this issue of Molecular Microbiology.