Cycling of RNAs on Hfq

The RNA chaperone Hfq is a key player in small RNA (sRNA)-mediated regulation of target mRNAs in many bacteria. The absence of this protein causes pleiotropic phenotypes such as impaired stress regulation and, occasionally, loss of virulence. Hfq promotes rapid sRNA-target mRNA base pairing to allow for fast, adaptive responses. For this to happen, sRNAs and/or mRNAs must be bound by Hfq. However, when the intra- or extracellular environment changes, so does the intracellular RNA pool, and this, in turn, requires a correspondingly rapid change in the pool of Hfq-bound RNAs. Biochemical studies have suggested tight binding of Hfq to many RNAs, indicating very slow dissociation rates. In contrast, the changing pool of binding-competent RNAs must compete for access to this helper protein in a minute time frame (known response time for regulation). How rapid exchange of RNAs on Hfq in vivo can be reconciled with biochemically stable and very slowly dissociating Hfq-RNA complexes is the topic of this review. Several recent reports suggest that the time scale discrepancy can be resolved by an "active cycling" model: rapid exchange of RNAs on Hfq is not limited by slow intrinsic dissociation rates, but is driven by the concentration of free RNA. Thus, transient binding of competitor RNA to Hfq-RNA complexes increases cycling rates and solves the strong binding/high turnover paradox.