The L box regulon: Lysine sensing by leader RNAs of bacterial lysine biosynthesis genes

Grundy, Frank J.; Lehman, Susan C.; Henkin, Tina M.

doi:10.1073/pnas.2133705100

Cited by 169 publications

(162 citation statements)

References 28 publications

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“…This divergence is readily observed with riboswitch elements that are found in both groups of organisms but regulate by different mechanisms depending on the host (e.g., the lysine-binding L box riboswitch; ref. 31). The S MK box, which is found only in the Lactobacillales group of low GϩC Gram-positive bacteria, is unusual in that it appears to function only at the level of translation.…”

Section: Discussionmentioning

confidence: 99%

S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S _MK box translational riboswitch RNA

Fuchs

Grundy

Henkin

2007

Proc. Natl. Acad. Sci. U.S.A.

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The SMK box is a conserved riboswitch motif found in the 5 untranslated region of metK genes [encoding S-adenosylmethionine (SAM) synthetase] in lactic acid bacteria, including Enterococcus, Streptococcus, and Lactococcus sp. Previous studies showed that this RNA element binds SAM in vitro, and SAM binding causes a structural rearrangement that sequesters the Shine-Dalgarno (SD) sequence by pairing with an anti-SD (ASD) element. A model was proposed in which SAM binding inhibits metK translation by preventing binding of the ribosome to the SD region of the mRNA. In the current work, the addition of SAM was shown to inhibit binding of 30S ribosomal subunits to S MK box RNA; in contrast, the addition of S-adenosylhomocysteine (SAH) had no effect. A mutant RNA, which has a disrupted SD-ASD pairing, was defective in SAM binding and showed no reduction of ribosome binding in the presence of SAM, whereas a compensatory mutation that restored SD-ASD pairing restored the response to SAM. Primer extension inhibition assays provided further evidence for SD-ASD pairing in the presence of SAM. These results strongly support the model that S MK box translational repression operates through occlusion of the ribosome binding site and that SAM binding requires the SD-ASD pairing.regulatory RNA ͉ RNA structure ͉ translational control ͉ SAM synthetase M any regulatory mechanisms have been discovered recently in bacteria in which RNA transcripts sense a regulatory signal (1-6). These regulatory RNAs, usually called RNA sensors or riboswitches, act in cis to regulate expression of the downstream coding sequence(s) without a requirement for regulatory proteins. Typically, the regulatory signal is an effector molecule (tRNA, noncoding RNA, or small molecule) that binds the nascent RNA transcript, causing a change in the RNA structure. In many systems of this type, the structural change either causes or prevents formation of the helix of an intrinsic transcriptional terminator (reviewed in 1, 4). Similar structural rearrangements can sequester the ribosome binding site (RBS) to regulate at the level of translation initiation (7-9). Binding of the effector to the RNA can also catalyze self-cleavage of the RNA transcript, as in the glmS system (10). Thermosensor riboswitches, in contrast, have no effector binding domain but simply respond by temperature-dependent modulation of the RNA structure (11-13). Riboswitches generally exhibit conserved sequence and structural elements that are responsible for high specificity for their cognate molecular signal.Many members of the Bacillus/Clostridium group of bacteria use the S box riboswitch system to control expression of genes involved in methionine metabolism (14). Included in this regulon is the metK gene, which encodes S-adenosylmethionine (SAM) synthetase, the enzyme responsible for the synthesis of SAM from methionine and ATP. The S box system uses SAM as the effector molecule both in vivo (15, 16) and in vitro (15, 17, 18), and regulation occurs primarily at the level of premature termi...

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Section: Discussionmentioning

confidence: 99%

S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S _MK box translational riboswitch RNA

Fuchs

Grundy

Henkin

2007

Proc. Natl. Acad. Sci. U.S.A.

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“…The importance of amino acids in protein biosynthesis and their catabolic use as an alternative energy source in bacteria make it necessary to control the level of amino acids in response to environmental and cellular changes (Serganov and Patel 2009). Three riboswitches have been identified to date that control amino acid concentrations in bacteria: the lysine, glycine, and S-adenosylmethionine (SAM)-responsive riboswitches (Grundy et al 2003;Sudarsan et al 2003;Winkler et al 2003;. Two of these, the lysine and glycine riboswitches, can directly detect amino acids.…”

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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“…The lysine riboswitch was first characterized in Bacillus subtilis, where it is located upstream of a lysine transporter (yvsH) and a lysine-sensitive aspartokinase (lysC) (7)(8)(9). Sequence alignments predicted that the secondary structure of the aptamer domain is arranged around a five-way junction that is important for aptamer architecture (7,9).…”

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Dual-acting riboswitch control of translation initiation and mRNA decay

Caron

Bastet

Lussier

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

148

150

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Riboswitches are mRNA regulatory elements that control gene expression by altering their structure in response to specific metabolite binding. In bacteria, riboswitches consist of an aptamer that performs ligand recognition and an expression platform that regulates either transcription termination or translation initiation. Here, we describe a dual-acting riboswitch from Escherichia coli that, in addition to modulating translation initiation, also is directly involved in the control of initial mRNA decay. Upon lysine binding, the lysC riboswitch adopts a conformation that not only inhibits translation initiation but also exposes RNase E cleavage sites located in the riboswitch expression platform. However, in the absence of lysine, the riboswitch folds into an alternative conformation that simultaneously allows translation initiation and sequesters RNase E cleavage sites. Both regulatory activities can be individually inhibited, indicating that translation initiation and mRNA decay can be modulated independently using the same conformational switch. Because RNase E cleavage sites are located in the riboswitch sequence, this riboswitch provides a unique means for the riboswitch to modulate RNase E cleavage activity directly as a function of lysine. This dual inhibition is in contrast to other riboswitches, such as the thiamin pyrophosphate-sensing thiM riboswitch, which triggers mRNA decay only as a consequence of translation inhibition. The riboswitch control of RNase E cleavage activity is an example of a mechanism by which metabolite sensing is used to regulate gene expression of single genes or even large polycistronic mRNAs as a function of environmental changes.gene regulation | RNA degradosome | translational control S ince the first demonstration that translation attenuation regulates the expression of the tryptophan operon (1), accumulating evidence has revealed the importance of posttranscriptional regulation in prokaryotes and eukaryotes alike. Posttranscriptional regulators include RNA molecules that operate through several mechanisms to control a wide range of physiological responses (2). Among newly identified RNA regulators are riboswitches, which are located in untranslated regions of several mRNAs and that modulate gene expression at the level of transcription, translation, or splicing (3). Riboswitches are highly structured regulatory domains that directly sense cellular metabolites such as amino acids, carbohydrates, coenzymes, and nucleobases. These genetic switches are composed of two modular domains consisting of an aptamer and an expression platform. The aptamer is involved in the specific recognition of the metabolite, and the expression platform is used to control gene expression by altering the structure of the mRNA. Recent bioinformatic analyses have reported the existence of several new RNA motifs exhibiting unconventional expression platforms (4, 5), suggesting that riboswitches using different regulation mechanisms are still likely to be discovered (6).The lysine riboswitch was first...

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The L box regulon: Lysine sensing by leader RNAs of bacterial lysine biosynthesis genes

Cited by 169 publications

References 28 publications

S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S _MK box translational riboswitch RNA

S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S _MK box translational riboswitch RNA

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

Dual-acting riboswitch control of translation initiation and mRNA decay

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The L box regulon: Lysine sensing by leader RNAs of bacterial lysine biosynthesis genes

Cited by 169 publications

References 28 publications

S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S MK box translational riboswitch RNA

S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S MK box translational riboswitch RNA

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

Dual-acting riboswitch control of translation initiation and mRNA decay

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S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S _MK box translational riboswitch RNA

S -adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the S _MK box translational riboswitch RNA