Unraveling RNA dynamical behavior of TPP riboswitches: a comparison between Escherichia coli and Arabidopsis thaliana

Antunes, Deborah; Jorge, Natasha Andressa Nogueira; Costa, Maurício G. S.; Passetti, Fábio; Caffarena, Ernesto R.

doi:10.1038/s41598-019-40875-1

Cited by 20 publications

(30 citation statements)

References 52 publications

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“…They are extensively studied in prokaryotic cells due to their high abundance and outstanding contribution to directing transcription and translation in various metabolic, physiological, and pathological pathways [ 45 ]. The only known class of eukaryotic riboswitches found in fungi, archaea and plants resides within intronic regions of TPP metabolism genes and fine-tunes their AS and expression in response to TPP binding ( Figure 1 c) [ 52 , 152 , 153 , 154 , 155 , 156 ].…”

Section: Cellular Modulators Of Rna Structurementioning

confidence: 99%

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

Taylor

Sobczak

2020

IJMS

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Alternative splicing is a highly sophisticated process, playing a significant role in posttranscriptional gene expression and underlying the diversity and complexity of organisms. Its regulation is multilayered, including an intrinsic role of RNA structural arrangement which undergoes time- and tissue-specific alterations. In this review, we describe the principles of RNA structural arrangement and briefly decipher its cis- and trans-acting cellular modulators which serve as crucial determinants of biological functionality of the RNA structure. Subsequently, we engage in a discussion about the RNA structure-mediated mechanisms of alternative splicing regulation. On one hand, the impairment of formation of optimal RNA structures may have critical consequences for the splicing outcome and further contribute to understanding the pathomechanism of severe disorders. On the other hand, the structural aspects of RNA became significant features taken into consideration in the endeavor of finding potential therapeutic treatments. Both aspects have been addressed by us emphasizing the importance of ongoing studies in both fields.

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Section: Cellular Modulators Of Rna Structurementioning

confidence: 99%

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

Taylor

Sobczak

2020

IJMS

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“…Therefore, we wondered whether an integrated analysis of overall network properties (eg, node centralities) in the context of the suboptimal paths would enable a deeper understanding of allostery in catK. A recent study revealed that the distributions of centralities obtained from communicating paths differ from those extracted from the overall network 71 . However, no attempt was made to compare the distributions of centralities obtained from other paths exhibiting similar lengths.…”

Section: Discussionmentioning

confidence: 99%

“…those extracted from the overall network. 71 However, no attempt was made to compare the distributions of centralities obtained from other paths exhibiting similar lengths. To overcome this bias, we designed a protocol to compare critical residues from allosteric sites with a decoy set composed of residues equally distant from the sink node (Figure 1).…”

Section: Searching For Other Catk Pockets Displaying Allosteric Potmentioning

confidence: 99%

Identification of potential allosteric binding sites in cathepsin K based on intramolecular communication

2020

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Network theory methods and molecular dynamics (MD) simulations are accepted tools to study allosteric regulation. Indeed, dynamic networks built upon correlation analysis of MD trajectories provide detailed information about communication paths between distant sites. In this context, we aimed to understand whether the efficiency of intramolecular communication could be used to predict the allosteric potential of a given site. To this end, we performed MD simulations and network theory analyses in cathepsin K (catK), whose allosteric sites are well defined. To obtain a quantitative measure of the efficiency of communication, we designed a new protocol that enables the comparison between properties related to ensembles of communication paths obtained from different sites. Further, we applied our strategy to evaluate the allosteric potential of different catK cavities not yet considered for drug design. Our predictions of the allosteric potential based on intramolecular communication correlate well with previous catK experimental and theoretical data. We also discuss the possibility of applying our approach to other proteins from the same family.

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“…They act in the recognition and post-transcriptional regulation of specific metabolites, controlling the expression of genes related to their respective ligands’ synthesis and transport [ 1 , 3 , 4 ]. A riboswitch recognizes a particular metabolite and is responsible for gene regulation [ 5 , 6 ]. In addition, most of the riboswitches work by negative feedback, and their respective metabolites are sometimes essential for the organism’s maintenance [ 3 , 6–8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, over 40 riboswitches have been identified in bacteria, although the thiamine pyrophosphate (TPP) riboswitch stands out as the only class identified so far for eukaryotic organisms [ 5 , 6 , 13 , 14 ]. The TPP riboswitch recognizes the metabolite and regulates biosynthesis or transport of TPP (or its precursors) in a wide variety of organisms distributed among the three domains of life [ 5 , 10 , 14 ]. The metabolite TPP is a bioactive derivative of thiamine, composed of two moieties synthesized independently: thiazole (THZ) and pyrimidine (HMP) [ 13 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

In silico investigation of riboswitches in fungi: structural and dynamical insights into TPP riboswitches in Aspergillus oryzae

Vargas-Junior¹,

Antunes

Guimarães

et al. 2022

RNA Biology

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Riboswitches are RNA sensors affecting post-transcriptional processes through their ability to bind to small molecules. Thiamine pyrophosphate (TPP) riboswitch plays a crucial role in regulating genes involved in synthesizing or transporting thiamine and phosphorylated derivatives in bacteria, archaea, plants, and fungi. Although TPP riboswitch is reasonably well known in bacteria, there is a gap in the knowledge of the fungal TPP riboswitches structure and dynamics, involving mainly sequence variation and TPP interaction with the aptamers. On the other hand, the increase of fungal infections and antifungal resistance raises the need for new antifungal therapies. In this work, we used computational approaches to build three-dimensional models for the three TPP riboswitches identified in Aspergillus oryzae , in which we studied their structure, dynamics, and binding free energy change (ΔG bind ) with TPP. Interaction patterns between the TPP and the surrounding nucleotides were conserved among the three models, evidencing high structural conservation. Furthermore, we show that the TPP riboswitch from the A. oryzae NMT1 gene behaves similarly to the E. coli thiA gene concerning the ΔG bind . In contrast, mutations in the fungal TPP riboswitches from THI4 and the nucleoside transporter genes led to structural differences, affecting the binding-site volume, hydrogen bond occupancy, and ΔG bind . Besides, the number of water molecules surrounding TPP influenced the ΔG bind considerably. Notably, our ΔG bind estimation agreed with previous experimental data, reinforcing the relationship between sequence conservation and TPP interaction.

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Unraveling RNA dynamical behavior of TPP riboswitches: a comparison between Escherichia coli and Arabidopsis thaliana

Cited by 20 publications

References 52 publications

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

Identification of potential allosteric binding sites in cathepsin K based on intramolecular communication

In silico investigation of riboswitches in fungi: structural and dynamical insights into TPP riboswitches in Aspergillus oryzae

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