An RNA Sensor for Intracellular Mg2+

Cromie, Michael J.; Shi, Yixin; Latifi, Tammy; Groisman, Eduardo A.

doi:10.1016/j.cell.2006.01.043

Cited by 293 publications

(401 citation statements)

References 47 publications

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“…Therefore, it was surprising to find that Mg 2+ homeostasis in Salmonella enterica and in Bacillus subtilis are controlled directly by two different RNA sensors located in the Mg 2+ transporter MgtA and MgtE mRNAs, respectively [18,19]. Under high Mg 2+ concentration, both sensors adapt one of two alternative conformations that arrest transcriptional elongation, using an as yet uncharacterized mechanism for the mgtA switch, and by a transcription attenuation mechanism for the mgtE switch ( Fig.…”

Section: Interactions Of Small Molecules With Higher-order Mrna Strucmentioning

confidence: 99%

Towards deciphering the principles underlying an mRNA recognition code

Serganov

Patel

2008

Current Opinion in Structural Biology

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Messenger RNAs interact with a number of different molecules that determine the fate of each transcript and contribute to the overall pattern of gene expression. These interactions are governed by specific mRNA signals, which in principle could represent a special mRNA recognition 'code'. Both, small molecules and proteins demonstrate a diversity of mRNA binding modes often dependent on the structural context of the regions surrounding specific target sequences. In this review, we have highlighted recent structural studies that illustrate the diversity of recognition principles used by mRNA binders for timely and specific targeting and processing of the message.

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Section: Interactions Of Small Molecules With Higher-order Mrna Strucmentioning

confidence: 99%

Towards deciphering the principles underlying an mRNA recognition code

Serganov

Patel

2008

Current Opinion in Structural Biology

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“…Based on the current number of orphan riboswitches and the genes they regulate, the repertoire of ligands for riboswitches should expand within and beyond small organic molecules. As an example of a potential non-metabolite ligand, levels of intracellular metal ions have been proposed to regulate the expression of the Salmonella enterica mgtA gene via an RNA element located within its 5′ UTR [63]. Additionally, a broadly distributed orphan riboswitch class appears to regulate the expression of an MgtE-family magnesium transporter (ykoK) in Bacillus subtilis as well as many genes responsible for metal uptake in other organisms [64,65], allowing one to wonder whether multiple classes of RNAs could function as metal ion sensors.…”

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confidence: 99%

Structural features of metabolite-sensing riboswitches

Wakeman

Winkler

Dann

2007

Trends in Biochemical Sciences

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Riboswitches, metabolite-sensing RNA elements found in untranslated regions of the transcripts they regulate, possess extensive tertiary structure to couple metabolite binding to genetic control. Herein, we discuss recently published structures from four riboswitch classes and compare these natural RNA structures to those of in vitro selected RNA aptamers, which bind similar ligands to those of the riboswitches. Additionally, we examine the glmS riboswitch, the first example of a ribozyme-based riboswitch. This RNA provides the latest twist in the riboswitch field and portends exciting advances in the coming years. Our knowledge of the mechanisms of genetic regulation by riboswitches has increased mightily in recent years and will continue to grow as new riboswitch classes and ligands are discovered and structurally characterized. KeywordsRNA structure; riboswitch; ribozyme; transcription attenuation; noncoding RNAs; posttranscriptional regulation; crystallography; NMR Riboswitches: Remnants of an ancient mode of genetic regulation?The "central dogma" states that information is stored as DNA, transcribed into RNA, and translated into proteins, which are traditionally thought to satisfy most cellular structural and catalytic requirements. Genetic control of these steps is believed to occur primarily through the action of regulatory proteins; however, the importance of noncoding RNAs in these processes has become increasingly appreciated in recent years [1]. In eubacterial organisms, regulatory RNAs can elicit control of gene expression through regulation of transcription attenuation, translation initiation [reviewed in 2,3], or mRNA stability [4]. These eubacterial regulatory RNAs function via diverse intermolecular (trans) or intramolecular (cis) mechanisms to regulate the target mRNA. Trans-acting regulatory RNAs interact with target mRNAs to control translation, mRNA stability, or transcription termination [reviewed in 5,6, 7], whereas others regulate gene expression through specific sequestration of RNA-binding proteins [8]. Cis-acting RNAs, which are the focus of this review, are located within untranslated regions (UTRs) of the mRNA transcript that they regulate. Genetic control by the latter RNA elements can be accomplished either through the sole action of the RNA molecule or in conjunction with recruited protein factors.A classic example of a cis-acting regulatory RNA is the transcription attenuation control of tryptophan biosynthesis genes in certain Gram-negative bacteria [9]. For this mechanism, the kinetics of translation of a short leader peptide dictates the conformational state of the overall 5′-UTR. Under tryptophan-depleted conditions the translating ribosome stalls at tryptophan codons within the leader peptide thereby allowing for formation of an antiterminator helix and [24-26; reviewed in 27,12]. Given their ability to function as sensitive sentinels for intracellular metabolites in a protein-independent manner, these RNAs are likely to require exquisite structural sophistication....

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“…The glycine riboswitch is the only known example that uses a cooperative binary system to bind its ligand. Furthermore, glycine is the smallest and simplest organic ligand known to be recognized by an RNA aptamer (Cromie et al 2006). The tandem aptamer arrangement used to bind and recognize glycine raises many molecular and cellular questions as to how the riboswitch senses a small change in glycine concentration to achieve cooperative ligand binding that results in altered gene activation and repression.…”

Section: Introductionmentioning

confidence: 99%

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Erion¹,

Strobel²

2010

RNA

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The glycine riboswitch has a tandem dual aptamer configuration, where each aptamer is a separate ligand-binding domain, but the aptamers function together to bind glycine cooperatively. We sought to understand the molecular basis of glycine riboswitch cooperativity by comparing sites of tertiary contacts in a series of cooperative and noncooperative glycine riboswitch mutants using hydroxyl radical footprinting, in-line probing, and native gel-shift studies. The results illustrate the importance of a direct or indirect interaction between the P3b hairpin of aptamer 2 and the P1 helix of aptamer 1 in cooperative glycine binding. Furthermore, our data support a model in which glycine binding is sequential; where the binding of glycine to the second aptamer allows tertiary interactions to be made that facilitate binding of a second glycine molecule to the first aptamer. These results provide insight into cooperative ligand binding in RNA macromolecules.

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An RNA Sensor for Intracellular Mg2+

Cited by 293 publications

References 47 publications

Towards deciphering the principles underlying an mRNA recognition code

Towards deciphering the principles underlying an mRNA recognition code

Structural features of metabolite-sensing riboswitches

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

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