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Hfq is a bacterial post-transcriptional regulator that modulates RNA structure, acting as a RNA chaperone. The most well-characterized function of Hfq is its role as a RNA matchmaker, promoting interactions between trans-encoded sRNAs (small regulatory RNAs) and their messenger RNAs (mRNAs) targets, leading translation and RNA stability regulation (Santos et al., 2019). In Bacteria sRNAs are critical for bacterial survival under adverse conditions and expression of virulence factors. Trans-encoded sRNAs are a large class of this regulators that are transcribed from a different locus than their targets and act as a imperfect base pairing, often regulating multiple mRNA (Faner & Feig, 2014).

There are several mechanisms to Hfq-mediated regulation. Most of the Hfq/RNAs/RNAm interactions described report inhibition of translation, although there are cases of positive regulation (Santos et al., 2019). Hfq can suppress protein synthesis by aiding the sRNA to bind the 5’ region of its target mRNA turning this region inaccessible to translation initiation. In the other way, this RNA chaperone can also act boosting translation, where sRNA guided by Hfq can bind in the 5’ region of the mRNA, changing its structure that otherwise inhibits ribosome binding. Hfq can also present a sRNA to its mRNA target leading to both degradation (Vogel & Luisi, 2011). It also has been shown that Hfq can interacts with either RNAs or RNAm independently, not just between this molecules. Hfq can modulate mRNA stability by directly binding and remodeling without the sRNA. It can also promotes the polyadenylation at the 3’ end of mRNAs, which in turn triggers 3’ to 5’ degradation by a exoribonuclease. The Hfq association also protects sRNAs from degradative activity of polynucleotide phosphorylase (PNPase) and ribonuclease E (RNase E) (Vogel & Luisi, 2011; Santos et al., 2019).

 

 

Recently, the discovery of others binding substrates with Hfq has expanded the regulatory spectrum of this protein. It was found that this RNA chaperone can also bind with rRNA and tRNA. Studies have shown that Hfq promotes ribosome assembly in bacteria, where this protein is required for the processing of pre-16S and folding of the mature 16S rRNA in E. coli, displaying Hfq as a important ribosome biogenesis factor in bacterias. This process seems to be independent of Hfq interactions with sRNAs, which the binding surfaces of the vast majority of the Hfq-dependent sRNAs are the proximal and rim faces, and for the rRNA, in the distal face of the Hfq. The same was observed for tRNA, where Hfq was also associated as a important pre-tRNA maturation factor, however, the binding of the structural elements of tRNAs occurs through the proximal face of Hfq (Santos et al., 2019).

Notably, the regulatory activity of Hfq is not restricted to RNAs, it was also found to bind DNA and protein. Hfq seems to act as a important factor in chromosome structure, forming a fiber like structure that leads, indirectly, to chromosome compaction through a mechanism still elusive. It is also associated with regulation of cellular replication and transfer of several transposon systems (Santos et al., 2019). There is also evidence that Hfq may engage in protein-protein interactions with PNPase, RNase E, poly(A) polymerase, RNA polymerase, transcription terminator Rho and ribosomal protein S12 of the 30S ribosomal subunit (Faner & Feig, 2014; Santos et al., 2019).