Dataset Information

The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation.

ABSTRACT: The T-box riboswitch is a unique, RNA-based regulatory mechanism that modulates expression of a wide variety of amino acid-related genes, predominantly in Firmicutes. RNAs of this class selectively bind a specific cognate tRNA, utilizing recognition of the tRNA anticodon and other tRNA features. The riboswitch monitors the aminoacylation status of the tRNA to induce expression of the regulated downstream gene(s) at the level of transcription antitermination or derepression of translation initiation in response to reduced tRNA charging via stabilization of an antiterminator or antisequestrator. Recent biochemical and structural studies have revealed new features of tRNA recognition that extend beyond the initially identified Watson-Crick base-pairing of a codon-like sequence in the riboswitch with the tRNA anticodon, and residues in the antiterminator or antisequestrator with the tRNA acceptor end. These studies have revealed new tRNA contacts and new modes of riboswitch function and ligand recognition that expand our understanding of RNA-RNA recognition and the biological roles of tRNA.

SUBMITTER: Kreuzer KD

PROVIDER: S-EPMC6329474 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation.

Kreuzer Kiel D KD Henkin Tina M TM

Microbiology spectrum 20180701 4

The T-box riboswitch is a unique, RNA-based regulatory mechanism that modulates expression of a wide variety of amino acid-related genes, predominantly in <i>Firmicutes</i>. RNAs of this class selectively bind a specific cognate tRNA, utilizing recognition of the tRNA anticodon and other tRNA features. The riboswitch monitors the aminoacylation status of the tRNA to induce expression of the regulated downstream gene(s) at the level of transcription antitermination or derepression of translation ...[more]

PMID: 30051797

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Project description:In Gram-positive bacteria, T-box riboswitches regulate the expression of aminoacyl-tRNA synthetases and other proteins in response to fluctuating transfer RNA aminoacylation levels under various nutritional states. T-boxes reside in the 5'-untranslated regions of the messenger RNAs they regulate, and consist of two conserved domains. Stem I contains the specifier trinucleotide that base pairs with the anticodon of cognate tRNA. 3' to stem I is the antiterminator domain, which base pairs with the tRNA acceptor end and evaluates its aminoacylation state. Despite high phylogenetic conservation and widespread occurrence in pathogens, the structural basis of tRNA recognition by this riboswitch remains ill defined. Here we demonstrate that the ~100-nucleotide T-box stem I is necessary and sufficient for specific, high-affinity (dissociation constant (Kd) ~150 nM) tRNA binding, and report the structure of Oceanobacillus iheyensis glyQ stem I in complex with its cognate tRNA at 3.2 Å resolution. Stem I recognizes the overall architecture of tRNA in addition to its anticodon, something accomplished by large ribonucleoproteins such as the ribosome, or proteins such as aminoacyl-tRNA synthetases, but is unprecedented for a compact mRNA domain. The C-shaped stem I cradles the L-shaped tRNA, forming an extended (1,604 Å(2)) intermolecular interface. In addition to the specifier-anticodon interaction, two interdigitated T-loops near the apex of stem I stack on the tRNA elbow in a manner analogous to those of the J11/12-J12/11 motif of RNase P and the L1 stalk of the ribosomal E-site. Because these ribonucleoproteins and T-boxes are unrelated, this strategy to recognize a universal tRNA feature probably evolved convergently. Mutually induced fit of stem I and the tRNA exploiting the intrinsic flexibility of tRNA and its conserved post-transcriptional modifications results in high shape complementarity, which in addition to providing specificity and affinity, globally organizes the T-box to orchestrate tRNA-dependent transcription regulation.

Dataset Information

The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation.

Publications

The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation.

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