Bacterial RNA Degradosomes: Molecular Machines under Tight Control

Abstract

Bacterial RNA degradosomes are multienzyme molecular machines that act as hubs for post-transcriptional regulation of gene expression. The ribonuclease activities of these complexes require tight regulation, as they are usually essential for cell survival while potentially destructive. Recent studies have unveiled a wide variety of regulatory mechanisms including autoregulation, post-translational modifications, and protein compartmentalization. Recently, the subcellular organization of bacterial RNA degradosomes was found to present similarities with eukaryotic messenger ribonucleoprotein (mRNP) granules, membraneless compartments that are also involved in mRNA and protein storage and/or mRNA degradation. In this review, we present the current knowledge on the composition and targets of RNA degradosomes, the most recent developments regarding the regulation of these machineries, and their similarities with the eukaryotic mRNP granules.

Keywords: RNA degradation; RNA degradosome; RNA maturation; compartmentalization; mRNP granules; membraneless organelles; post-transcriptional regulation.

Figure 1.

Schematic representation of the core components of the different types of bacterial RNA degradosomes described to date. Solid arrows indicate interactions, dashed arrows possible additional partners. (a) E. coli RNA degradosome, based on RNase E. RNase E (green) possesses a C-terminal domain containing a membrane-targeting helix, as well as interaction sites for the RNA helicase RhlB, enolase (Eno) and polynucleotide phosphorylase (PNPase). Not shown are binding sites for RNA. (b) B. subtilis RNA degradosome, containing RNase Y and also RNases J1 and J2, that potentially interact with other enzymes, namely the RNA helicase CshA, PNPase, enolase and phosphofructokinase (Pfk). (c) H. pylori RNA degradosome, based on RNase J, that interacts with the RNA helicase RhpA. (d) M. tuberculosis possible RNA degradosome(s), containing either RNase J, RNase E or both, that interact with the RNA helicase RhlE and PNPase. The question mark indicates that the membrane targeting has not been explored so far.

Figure 2.

Distribution of the degradosome RNases (RNase E, RNase J and RNase Y) in a representative set of bacterial genomes. Most bacterial species (96.5%) contain at least one of these RNases. Out of the 54 genomes that do not contain any of these RNases (marked as “none” in the Venn diagram), 40 contain RNase G. Analysis was performed on 15S5 representative genomes chosen based on phylogenetic diversity as previously described [101], using the PubSEED database [102]. Details are provided in supplemental Table S1 and the results are also available in the ‘RNAse_2019_Minimal’ subsystem on the public PubSEED server (http://pubseed.theseed.org/SubsysEditor.cgi).

Figure 3, Key Figure.

Regulation mechanisms of the RNA degradosomes. These mechanisms are not mutually exclusive and may act in concert to adjust the activity of the RNA degradosome. There are five major classes of regulation (a) the components of the RNA degradosome are often autoregulated, and sometimes they also regulate the expression of each other, (b) the partners of the RNA degradosome are susceptible to post-translational modifications, often as a result of a phage infection causing phage RNA to be protected from degradation, (c) different proteins can bind the core RNA degradosome and regulate its activity, including some cellular proteins, ribosomal proteins, as well as dedicated bacterial or viral inhibitors, (d) the central RNases of some degradosomes are compartmentalized within the cell in the form of foci, and (e) the components of the RNA degradosome are often targeted to the bacterial membrane, forming foci or not.

Figure 4.

Models for the possible physiological roles of RNA degradosome foci. In (a) and (b), the foci represent a less active form of the RNA degradosome. In (a), the foci-forming degradosomes are catalytically inactive, whereas the complexes outside foci are able to degrade RNA. In (b), the foci-forming degradosomes retain their catalytic activity, but they are sequestered away from some cellular RNAs, limiting their degradation. In (c), the foci-forming degradosomes are the active form, making foci RNA degradation hubs, whereas the complexes outside foci retain comparatively little or no activity. The targeting mechanisms of the RNAs that are degraded by the degradosomes are still not clear.