Hfq

Hfq is a bacterial RNA-binding protein that acts as a global regulator of RNA metabolism. It belongs to the Sm-like (Sm) protein family and forms a homo-hexameric ring that binds various RNA species. Hfq was first identified as a host factor required for replication of RNA phage Qβ in Escherichia coli, but subsequent work established its central role in bacterial gene regulation through small regulatory RNAs (sRNAs).

Structure and RNA binding: The Hfq hexamer presents two RNA-binding surfaces, the proximal and distal faces, and a central pore. The proximal face preferentially binds U-rich regions of sRNAs, while the distal face recognizes A-rich sequences in target mRNAs. This arrangement enables Hfq to act as an RNA chaperone, promoting or stabilizing base-pairing between sRNAs and their mRNA targets and influencing translation initiation and mRNA stability. In many bacteria, Hfq also participates in recruiting the RNase E degradosome to sRNA–mRNA complexes, accelerating decay of the target.

Biological role and targets: Hfq is a global regulator of post-transcriptional gene expression. It modulates numerous pathways, including stress responses, metabolism, and virulence. Well-characterized examples include sRNAs such as RyhB, DsrA, and OxyS in enterobacteria, which control iron homeostasis, stress responses, and envelope function. Hfq is required for proper virulence in several pathogens and influences biofilm formation and quorum sensing.

Distribution and significance: Hfq homologs are widespread among bacteria, though presence and essentiality vary by lineage. Because many sRNA-mediated regulatory circuits depend on Hfq, the protein is a focal point in studies of RNA-based regulation and is considered a potential target for antimicrobial strategies that disrupt sRNA-mediated control of virulence and stress responses.