Bacterial small RNA-based negative regulation: Hfq and its accomplices

Abstract

A large group of bacterial small regulatory RNAs (sRNAs) use the Hfq chaperone to mediate pairing with and regulation of mRNAs. Recent findings help to clarify how Hfq acts and highlight the role of the endonuclease RNase E and its associated proteins (the degradosome) in negative regulation by these sRNAs. sRNAs frequently uncouple transcription and translation by blocking ribosome access to the mRNA, allowing other proteins access to the mRNA. As more examples of sRNA-mediated regulation are studied, more variations on how Hfq, RNase E, and other proteins collaborate to bring about sRNA-based regulation are being found.

FIGURE 1.

Important protein players in sRNA-mediated gene repression. A, faces of Hfq for RNA interactions, illustrating the proximal face of Hfq (orange) bound to sRNA (green), the distal face of Hfq (purple) bound to an mRNA target (blue), and the rim of Hfq (red), shown to have interactions with some sRNAs. The currently understood function of each face in sRNA-mediated regulation is summarized at the bottom of each panel. B, organization of the RNA degradosome in E. coli. The endonuclease RNase E consists of two domains. The N-terminal domain (residues 1–529) resembles RNase G and contains the catalytic site of the enzyme. The C-terminal domain (residues 530–1061) serves as a scaffold domain with which the other components of the degradosome associate to form an active complex. These components and the residues at which they have been shown to interact with RNase E are shown. Interactions of Hfq with RNase E regions closer to the C terminus have also been suggested. See text for references.

FIGURE 2.

Mechanisms of sRNA-mediated regulation. A, the coupling of transcription by RNA polymerase (green) and translation by the ribosome (blue) in the absence of sRNA regulation. Growing evidence suggests the possibility of interactions between RNA polymerase and the ribosome to ensure coupling (see text). B, sRNAs can block ribosome entry by pairing with sequences at or near the RBS of the mRNA. Pairing of the sRNA with the target mRNA is facilitated by Hfq (orange). As a result of blocking ribosome binding, the sRNA can decouple transcription and translation. Arrow 1, the unprotected mRNA may then be subject to cleavage by RNase E (yellow). Arrow 2, in addition to access to RNase E, the untranslated RNA can also provide a binding site for Rho (purple), leading to transcription termination. C, alternatively, sRNAs may induce cleavage of the mRNA by recruiting RNase E, causing mRNA cleavage without inhibiting translation. Recruitment of RNase E may be through interactions with Hfq, the RNAs, or both.