MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.

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Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens.

Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population.

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Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

Small RNAs are ubiquitously present regulators in all kingdoms of life. Most bacterial and archaeal small RNAs (sRNAs) act by antisense mechanisms on multiple target mRNAs, thereby globally affecting essentially any conceivable trait-stress responses, adaptive metabolic changes, virulence etc. The sRNAs display many distinct mechanisms of action, most of them through effects on target mRNA translation and/or stability, and helper proteins like Hfq often play key roles. Recent data highlight the interplay between posttranscriptional control by sRNAs and transcription factor-mediated transcriptional control, and cross talk through mutual regulation of regulators. Based on the properties that distinguish sRNA-type from transcription factors-type control, we begin to glimpse why sRNAs have evolved as a second, essential layer of gene regulation. This review will discuss the prevalence of sRNAs, who they are, what biological roles they play, and how they carry out their functions.

Small RNAs in bacteria and archaea: who they are, what they do, and how they do it

RNase E is an essential endonuclease that is abundant in many bacteria and plays an important part in all aspects of RNA metabolism. It functions as part of a large macromolecular complex known as the RNA degradosome. Recent evidence suggests that this complex associates with the inner membrane of bacteria, an observation that challenges traditional models in which soluble RNases are proposed to randomly interact with RNAs in the cytosol. In this Review, I summarize the major roles of RNase E in RNA processing and decay and discuss the various mechanisms that regulate its activity. I also propose a new model to rationalize the mechanism of RNase E action in the context of its localization in the bacterial cell.

RNase E: at the interface of bacterial RNA processing and decay

The Seed Region of a Small RNA Drives the Controlled Destruction of the Target mRNA by the Endoribonuclease RNase E

The bacterial endoribonuclease RNase E occupies a pivotal position in the control of gene expression, as its actions either commit transcripts to an irreversible fate of rapid destruction or unveil their hidden functions through specific processing. Moreover, the enzyme contributes to quality control of rRNAs. The activity of RNase E can be directed and modulated by signals provided through regulatory RNAs that guide the enzyme to specific transcripts that are to be silenced. Early in its evolutionary history, RNase E acquired a natively unfolded appendage that recruits accessory proteins and RNA. These accessory factors facilitate the activity of RNase E and include helicases that remodel RNA and RNA-protein complexes, and polynucleotide phosphorylase, a relative of the archaeal and eukaryotic exosomes. RNase E also associates with enzymes from central metabolism, such as enolase and aconitase. RNase E-based complexes are diverse in composition, but generally bear mechanistic parallels with eukaryotic machinery involved in RNA-induced gene regulation and transcript quality control. That these similar processes arose independently underscores the universality of RNA-based regulation in life. Here we provide a synopsis and perspective of the contributions made by RNase E to sustain robust gene regulation with speed and accuracy.

RNase E and the High-Fidelity Orchestration of RNA Metabolism

A crucial step in the production of proteins is the translation of messenger RNA molecules. Other RNA molecules called small RNAs are also involved in this process: these small RNAs bind to the messenger RNA molecules to either increase or decrease the production of proteins. Bacteria and other microorganisms use small RNA molecules to help them respond to stress conditions and to changes in their environment, such as fluctuations in temperature or the availability of nutrients. The ability to rapidly adapt to these changes enables bacteria to withstand harmful conditions and to make efficient use of resources available to them. Many small RNA molecules use a protein called Hfq to help them interact with their target messenger RNAs. In some cases this protein protects the small RNA molecules when they are not bound to their targets. Hfq also helps the small RNA to bind to the messenger RNA, and then recruits other enzymes that eventually degrade the complex formed by the different RNA molecules. Previous research has shown that six Hfq subunits combine to form a ring-shaped structure and has also provided some clues about the way in which Hfq can recognise a short stretch of a small RNA molecule, but the precise details of the interaction between them are not fully understood. Now Dimastrogiovanni et al. have used a technique called X-ray crystallography to visualize the interaction between Hfq and a small RNA molecule called RydC. These experiments reveal that a particular region of RydC adopts a structure known as a pseudoknot and that this structure is critical for the interactions between the RydC molecules and the Hfq ring. Dimastrogiovanni et al. find that one RydC molecule interacts with one Hfq ring, and they identify the contact points between the RydC molecule and different regions of the Hfq ring. Based on this information, Dimastrogiovanni et al. propose a model for how the RydC:Hfq complex is likely to interact with a messenger RNA molecule. The next step will be to test this model in experiments.

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Recognition of the small regulatory RNA RydC by the bacterial Hfq protein

The social fabric of the RNA degradosome.

RNA enables the material interpretation of genetic information through time and in space. The creation, destruction and activity of RNA must be well controlled and tightly synchronized with numerous cellular processes. We discuss here the pathways and mechanism of bacterial RNA turnover, and describe how RNA itself modulates these processes as part of decision-making networks. The central roles of RNA decay and other aspects of RNA metabolism in cellular control are also suggested by their vulnerability to sabotage by phages; nonetheless, RNA can be used in defense against phage infection, and these processes are described here. Salient aspects of RNA turnover are drawn together to suggest how it could affect complex effects such as phenotypic diversity in populations and responses that persist for multiple generations.

Katarzyna J Bandyra

Papers

The Seed Region of a Small RNA Drives the Controlled Destruction of the Target mRNA by the Endoribonuclease RNase E

RNase E and the High-Fidelity Orchestration of RNA Metabolism

Recognition of the small regulatory RNA RydC by the bacterial Hfq protein

The social fabric of the RNA degradosome.

Licensing and due process in the turnover of bacterial RNA.