Hfq and its constellation of RNA

Abstract

Hfq is an RNA-binding protein that is common to diverse bacterial lineages and has key roles in the control of gene expression. By facilitating the pairing of small RNAs with their target mRNAs, Hfq affects the translation and turnover rates of specific transcripts and contributes to complex post-transcriptional networks. These functions of Hfq can be attributed to its ring-like oligomeric architecture, which presents two non-equivalent binding surfaces that are capable of multiple interactions with RNA molecules. Distant homologues of Hfq occur in archaea and eukaryotes, reflecting an ancient origin for the protein family and hinting at shared functions. In this Review, we describe the salient structural and functional features of Hfq and discuss possible mechanisms by which this protein can promote RNA interactions to catalyse specific and rapid regulatory responses in vivo.Hfq was discovered in Escherichia coli nearly half a century ago (BOX 1) and was one of the first recognized representatives of an extensive RNA-binding protein family, the members of which can be found in almost every cellular organism from all three domains of life 1 . The meta-zoan homologues of Hfq include the Sm proteins, named after the autoimmune Sm antibodies that recognize them, and the closely related Sm-like (LSm) proteins, which are also found in single-celled eukaryotes and in archaea. The characteristic feature of the collective Hfq-Sm-LSm protein family is a ring-like, multimeric quaternary architecture that supports interactions with partner macromolecules. Both Hfq and the SmLSm proteins have general roles as RNA binders that contribute to post-transcriptional regulation. The Sm-LSm proteins include central components of the mRNA-splicing machinery, scaffolds for RNA-decapping assemblies, and protective chaperones of ribosomal RNAs, small nucleolar RNAs and tRNA precursors 1 .Competing interests statement The authors declare no competing financial interests. Today, Hfq is perceived primarily as the core component of a global post-transcriptional network, in which it facilitates the short and imperfect base-pairing interactions of regulatory small RNAs (sRNAs) with trans-encoded target mRNAs. Model organisms such as E. coli or Salmonella enterica can express ~100 different sRNAs. Unlike their functional equivalents in eukaryotes -the 22-nucleotide-long microRNAs -these bacterial sRNAs are heterogeneous in size and structure. The intriguing physiological functions of Hfq and sRNAs have recently been reviewed [2][3][4][5] . FURTHER INFORMATIONThere are several general mechanisms of Hfq-mediated regulation at the levels of translation or RNA stability [2][3][4][5][6][7] , and these are summarized in FIG. 1. First, Hfq can suppress protein synthesis by aiding a cognate sRNA to bind the 5′ region of its target mRNA, thus rendering this 5′ region inaccessible for translation initiation (FIG. 1a). Conversely, Hfq can boost translation by guiding an sRNA to the 5′ region of its target mRNA in order to disrupt a secondary str...

Dual RNA-seq of pathogen and host

“…Typically regulation is mediated by base-pairing between the so-called seed region of the sRNA and critical sites in the mRNA target -in the classical scenario the ribosome binding site, thereby preventing translation initiation and inducing mRNA decay. For this to occur, many sRNAs rely on a chaperone protein, referred to as Hfq (host factor of the RNA bacteriophage Qβ) (Vogel and Luisi, 2011). Hfq facilitates inter-molecular RNA-RNA interactions, recruits specific ribonucleases for target mRNA degradation and protects the bound sRNA from being nucleolytically attacked, thereby increasing its stability (Wagner, 2013).…”

“…Since STnc440 associates with Hfq Sittka et al, 2008), it is likely to regulate mRNAs by base pairing (Vogel and Luisi, 2011). Thus, in order to identify direct targets of this sRNA, a previously described pulse-expression approach was applied (Masse et al, 2005;Papenfort et al, 2006).…”

Cold-shock RNA-binding protein CspR is also exposed to the surface of Enterococcus faecalis

“…However, it has been shown that other RNA-binding proteins, e.g. the welldocumented Hfq, have a role in the regulation of the expression of genes involved in virulence (Brennan & Link, 2007;Chao & Vogel, 2010; Christiansen et al, 2004;Vogel & Luisi, 2011). Of note, enterococci and streptococci do not harbour hfq-like genes (Sun et al, 2002).…”

Anti-virulence Strategies to Target Bacterial Infections

“…Hfq is known as the central mediator of sRNA-based gene regulation in bacteria as it establishes dynamic interactions of a wide range of RNA molecules and manipulates translation and degradation of many mRNAs important for pathogenesis (Chao and Vogel 2010;Vogel and Luisi 2011). In fact, hfq knock-out derivatives of many important pathogens (e.g.…”