New aspects of RNA-based regulation by Hfq and its partner sRNAs

•Novel cross-linking and sequencing methods uncover new sRNAs and sRNA networks.•Many sRNAs are encoded within the 3′ and 5′ UTRs of mRNA as well as elsewhere.•sRNA availability can be regulated post-transcriptionally by decoy and sponge RNAs.•Hfq can regulate mRNA translation without sRNAs, alone and with other proteins.•Some sRNAs that use Hfq also bind and regulate translational repressor CsrA. Hfq, an RNA chaperone, promotes the pairing of small RNAs (sRNAs) to target mRNAs, mediating post-transcriptional regulation of mRNA stability and translation. This regulation contributes to bacterial adaptation during stress and pathogenesis. Recent advances in sequencing techniques demonstrate the presence of sRNAs encoded not only in intergenic regions but also from the 3′ and 5′ UTRs of mRNAs, expanding sRNA regulatory networks. Additional layers of regulation by Hfq and its associated RNAs continue to be found. Newly identified RNA sponges modulate the activity of some sRNAs. A subset of sRNAs are proving to be bifunctional, able to pair with targets and also encoding small ORFs or binding other RNA binding proteins, such as CsrA. In addition, there are accumulating examples of Hfq inhibiting mRNA translation in the absence of sRNAs.