Cyclic di-guanosine monophosphate (di-GMP) is a circular RNA dinucleotide that functions as a second messenger in diverse species of bacteria to trigger wide-ranging physiological changes, including ...cell differentiation, conversion between motile and biofilm lifestyles, and virulence gene expression. However, the mechanisms by which cyclic di-GMP regulates gene expression have remained a mystery. We found that cyclic di-GMP in many bacterial species is sensed by a riboswitch class in messenger RNA that controls the expression of genes involved in numerous fundamental cellular processes. A variety of cyclic di-GMP regulons are revealed, including some riboswitches associated with virulence gene expression, pilus formation, and flagellum biosynthesis. In addition, sequences matching the consensus for cyclic di-GMP riboswitches are present in the genome of a bacteriophage.
Riboswitches and the RNA world Breaker, Ronald R
Cold Spring Harbor perspectives in biology,
02/2012, Letnik:
4, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Riboswitches are structured noncoding RNA domains that selectively bind metabolites and control gene expression (Mandal and Breaker 2004a; Coppins et al. 2007; Roth and Breaker 2009). Nearly all ...examples of the known riboswitches reside in noncoding regions of messenger RNAs where they control transcription or translation. Newfound classes of riboswitches are being reported at a rate of about three per year (Ames and Breaker 2009), and these have been shown to selectively respond to fundamental metabolites including coenzymes, nucleobases or their derivatives, amino acids, and other small molecule ligands. The characteristics of some riboswitches suggest they could be modern descendents of an ancient sensory and regulatory system that likely functioned before the emergence of enzymes and genetic factors made of protein (Nahvi et al. 2002; Vitreschak et al. 2004; Breaker 2006). If true, then some of the riboswitch structures and functions that serve modern cells so well may accurately reflect the capabilities of RNA sensors and switches that existed in the RNA World. This article will address some of the characteristics of modern riboswitches that may be relevant to ancient versions of these metabolite-sensing RNAs.
An expanding number of metabolite-binding riboswitch classes are being discovered in the noncoding portions of bacterial genomes. Findings over the last decade indicate that bacteria commonly use ...these RNA genetic elements as regulators of metabolic pathways and as mediators of changes in cell physiology. Some riboswitches are surprisingly complex, and they rival protein factors in their structural and functional sophistication. Each new riboswitch discovery expands our knowledge of the biochemical capabilities of RNA, and some give rise to new questions that require additional study to be addressed. Some of the greatest prospects for riboswitch research and some of the more interesting mysteries are discussed in this review.
Riboswitches and Translation Control Breaker, Ronald R
Cold Spring Harbor perspectives in biology,
11/2018, Letnik:
10, Številka:
11
Journal Article
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A growing collection of bacterial riboswitch classes is being discovered that sense central metabolites, coenzymes, and signaling molecules. Included among the various mechanisms of gene regulation ...exploited by these RNA regulatory elements are several that modulate messenger RNA (mRNA) translation. In this review, the mechanisms of riboswitch-mediated translation control are summarized to highlight both their diversity and potential ancient origins. These mechanisms include ligand-gated presentation or occlusion of ribosome-binding sites, control of alternative splicing of mRNAs, and the regulation of mRNA stability. Moreover, speculation on the potential for novel riboswitch discoveries is presented, including a discussion on the potential for the discovery of a greater diversity of mechanisms for translation control.
More than 55 distinct classes of riboswitches that respond to small metabolites or elemental ions have been experimentally validated to date. The ligands sensed by these riboswitches are biased in ...favor of fundamental compounds or ions that are likely to have been relevant to ancient forms of life, including those that might have populated the "RNA World", which is a proposed biochemical era that predates the evolutionary emergence of DNA and proteins. In the following text, I discuss the various types of ligands sensed by some of the most common riboswitches present in modern bacterial cells and consider implications for ancient biological processes centered on the proven capabilities of these RNA-based sensors. Although most major biochemical aspects of metabolism are represented by known riboswitch classes, there are striking sensory gaps in some key areas. These gaps could reveal weaknesses in the performance capabilities of RNA that might have hampered RNA World evolution, or these could highlight opportunities to discover additional riboswitch classes that sense essential metabolites.
Gene regulation by riboswitches Mandal, Maumita; Breaker, Ronald R
Nature reviews. Molecular cell biology,
06/2004, Letnik:
5, Številka:
6
Journal Article
Recenzirano
Riboswitches are complex folded RNA domains that serve as receptors for specific metabolites. These domains are found in the non-coding portions of various mRNAs, where they control gene expression ...by harnessing allosteric structural changes that are brought about by metabolite binding. New findings indicate that riboswitches are robust genetic elements that are involved in regulating fundamental metabolic processes in many organisms.
Riboswitches are structured domains that usually reside in the noncoding regions of mRNAs, where they bind metabolites and control gene expression. Like their protein counterparts, these RNA gene ...control elements form highly specific binding pockets for the target metabolite and undergo allosteric changes in structure. Numerous classes of riboswitches are present in bacteria and they comprise a common and robust metabolite-sensing system.
A class of riboswitches that recognizes guanine and discriminates against other purine analogs was recently identified. RNAs that carry the consensus sequence and structural features of guanine ...riboswitches are located in the 5' untranslated region (UTR) of numerous prokaryotic genes, where they control the expression of proteins involved in purine salvage and biosynthesis. We report that three representatives of this riboswitch class bind adenine with values for apparent dissociation constant (apparent K(d)) that are several orders of magnitude lower than those for binding guanine. Because preference for adenine is attributable to a single nucleotide substitution, the RNA most likely recognizes its ligand by forming a Watson-Crick base pair. In addition, the adenine riboswitch associated with the ydhL gene of Bacillus subtilis functions as a genetic 'on' switch, wherein adenine binding causes a structural rearrangement that precludes formation of an intrinsic transcription terminator stem.
Riboswitches are structured elements typically found in the 5′ untranslated regions of mRNAs, where they regulate gene expression by binding to small metabolites. In all examples studied to date, ...these RNA control elements do not require the involvement of protein factors for metabolite binding. Riboswitches appear to be pervasive in eubacteria, suggesting that this form of regulation is an important mechanism by which metabolic genes are controlled. Recently discovered riboswitch classes have surprisingly complex mechanisms for regulating gene expression and new high-resolution structural models of these RNAs provide insight into the molecular details of metabolite recognition by natural RNA aptamers.
With continuing identification of novel structured noncoding RNAs, there is an increasing need to create schematic diagrams showing the consensus features of these molecules. RNA structural diagrams ...are typically made either with general-purpose drawing programs like Adobe Illustrator, or with automated or interactive programs specific to RNA. Unfortunately, the use of applications like Illustrator is extremely time consuming, while existing RNA-specific programs produce figures that are useful, but usually not of the same aesthetic quality as those produced at great cost in Illustrator. Additionally, most existing RNA-specific applications are designed for drawing single RNA molecules, not consensus diagrams.
We created R2R, a computer program that facilitates the generation of aesthetic and readable drawings of RNA consensus diagrams in a fraction of the time required with general-purpose drawing programs. Since the inference of a consensus RNA structure typically requires a multiple-sequence alignment, the R2R user annotates the alignment with commands directing the layout and annotation of the RNA. R2R creates SVG or PDF output that can be imported into Adobe Illustrator, Inkscape or CorelDRAW. R2R can be used to create consensus sequence and secondary structure models for novel RNA structures or to revise models when new representatives for known RNA classes become available. Although R2R does not currently have a graphical user interface, it has proven useful in our efforts to create 100 schematic models of distinct noncoding RNA classes.
R2R makes it possible to obtain high-quality drawings of the consensus sequence and structural models of many diverse RNA structures with a more practical amount of effort. R2R software is available at http://breaker.research.yale.edu/R2R and as an Additional file.
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