Figure 1: Mechanisms of Hfq-dependent regulation.

In general, binding of Hfq, with or without other partners (sRNAs in this figure) can change RNA folding and allow or block access of other RNA binding factors, therefore changing the fate of the mRNA.

A. sRNA Regulation of Translation Initiation and/or mRNA Decay.

Negative Regulation: In most cases, negative regulation is via sRNA pairing with targets, as shown here. This can lead to inhibition of translation (left panel), recruitment of RNases (right panel), or both (center panel). Hfq helps to stabilize and recruit the sRNA, and may, in some cases, help to recruit ribonucleases.

Positive Regulation: sRNAs and Hfq binding can collaborate to change RNA folding, remodeling an inhibitory hairpin, for instance, to allow ribosome access (left and center panels), or blocking access of a ribonuclease such as RNase E (right panel), thus stabilizing an mRNA.

B. Regulation of Rho-Dependent Transcription Termination

Rho (purple hexamers) terminates transcription by first accessing naked RNA at a rut site (dotted yellow portion of mRNA), and then traveling along the elongating RNA to release the RNA from RNA polymerase (blue oval) (reviewed in [43]). Thus sRNAs that affect access to the rut site can regulate the ability of Rho to act.

Negative Regulation: Promoting Rho-Dependent Termination: In at least one case, sRNA pairing to a target blocks ribosome entry, allowing Rho to access the naked RNA and leading to Rho-dependent termination within the ORF, downstream of the pairing site [44].

Positive Regulation: Blocking Rho-Dependent Termination: sRNA binding may also block access of Rho to RNA, therefore allowing transcription of downstream genes. In the case examined, this positive regulation collaborates with remodeling of the 5’ UTR to allow both increased transcription and translation [45].