Multiple conformational states of riboswitches fine-tune gene regulation

Fürtig, Boris; Nozinovic, Senada; Reining, Anke; Schwalbe, Harald

doi:10.1016/j.sbi.2015.02.007

Cited by 58 publications

(48 citation statements)

References 57 publications

(54 reference statements)

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“…For intracellular riboswitch concentration, values between 1 to 100 nM have been estimated [75,76]. Together, this would result in [Mg 2+ ]:[RNA] ratios that embrace the critical [Mg 2+ ]:[RNA] ratio of ~20, above which the rigidifying effect towards the terminal ends of P1 is largest.…”

Section: Discussionmentioning

confidence: 99%

Ligand-mediated and tertiary interactions cooperatively stabilize the P1 region in the guanine-sensing riboswitch

Hanke

Gohlke

2017

PLoS ONE

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Riboswitches are genetic regulatory elements that control gene expression depending on ligand binding. The guanine-sensing riboswitch (Gsw) binds ligands at a three-way junction formed by paired regions P1, P2, and P3. Loops L2 and L3 cap the P2 and P3 helices and form tertiary interactions. Part of P1 belongs to the switching sequence dictating the fate of the mRNA. Previous studies revealed an intricate relationship between ligand binding and presence of the tertiary interactions, and between ligand binding and influence on the P1 region. However, no information is available on the interplay among these three main regions in Gsw. Here we show that stabilization of the L2-L3 region by tertiary interactions, and the ligand binding site by ligand binding, cooperatively influences the structural stability of terminal base pairs in the P1 region in the presence of Mg2+ ions. The results are based on molecular dynamics simulations with an aggregate simulation time of ~10 μs across multiple systems of the unbound state of the Gsw aptamer and a G37A/C61U mutant, and rigidity analyses. The results could explain why the three-way junction is a central structural element also in other riboswitches and how the cooperative effect could become contextual with respect to intracellular Mg2+ concentration. The results suggest that the transmission of allosteric information to P1 can be entropy-dominated.

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Section: Discussionmentioning

confidence: 99%

Ligand-mediated and tertiary interactions cooperatively stabilize the P1 region in the guanine-sensing riboswitch

Hanke

Gohlke

2017

PLoS ONE

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“…These features of stability and interchangeability ideally suit RNA for creating metastable structures that can switch gene expression on or off. Owing to the stability of the RNA double helix, RNA regulatory elements may be as small as a single stem-loop or anti-sense helix, or involve more elaborate tertiary structures (32–34). The potential simplicity of RNA-based regulation offers microbes an expedient means of evolving new regulatory circuits (35).…”

Section: Introductionmentioning

confidence: 99%

Proteins That Chaperone RNA Regulation

Woodson¹,

Panja²,

Santiago-Frangos

2018

Microbiol Spectr

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RNA-binding proteins chaperone the biological functions of non-coding RNA by reducing RNA misfolding, improving matchmaking between regulatory RNA and targets, and exerting quality control over RNP biogenesis. Recent studies of E. coli CspA, HIV NCp and E. coli Hfq, are beginning to show how RNA-binding proteins remodel RNA structures. These different protein families use common strategies for disrupting or annealing RNA double helices, which can be used to understand the mechanisms by which proteins chaperone RNA-dependent regulation in bacteria.

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“…Once thought to be noncatalytic messengers and scaffolds for use in translation, RNA has been shown to play active roles in such diverse processes as mRNA splicing (Kruger et al 1982;McNeil et al 2016), regulation of transcription (Grundy et al 1994;Henkin 1994;Serganov and Nudler 2013;Furtig et al 2015) and translation (Lee et al 1993;Wightman et al 1993;Filipowicz et al 2008), viral assembly (Zeffman et al 2000;Cantara et al 2014;Sardo et al 2015;Stockley et al 2016), and immunity (Brouns et al 2008;Zhang et al 2010;Dhahbi 2015;Cavalieri et al 2016). Many of these functions result from the ability of RNA to fold into complex secondary and tertiary structures.…”

Section: Introductionmentioning

confidence: 99%

RiboCAT: a new capillary electrophoresis data analysis tool for nucleic acid probing

Cantara

Hatterschide

et al. 2016

RNA

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Chemical and enzymatic probing of RNA secondary structure and RNA/protein interactions provides the basis for understanding the functions of structured RNAs. However, the ability to rapidly perform such experiments using capillary electrophoresis has been hampered by relatively labor-intensive data analysis software. While these computationally robust programs have been shown to calculate residue-specific reactivities to a high degree of accuracy, they often require time-consuming manual intervention and lack the ability to be easily modified by users. To alleviate these issues, RiboCAT (Ribonucleic acid capillaryelectrophoresis analysis tool) was developed as a user-friendly, Microsoft Excel-based tool that reduces the need for manual intervention, thereby significantly shortening the time required for data analysis. Features of this tool include (i) the use of an Excel platform, (ii) a method of intercapillary signal alignment using internal size standards, (iii) a peak-sharpening algorithm to more accurately identify peaks, and (iv) an open architecture allowing for simple user intervention. Furthermore, a complementary tool, RiboDOG (RiboCAT data output generator) was designed to facilitate the comparison of multiple data sets, highlighting potential inconsistencies and inaccuracies that may have occurred during analysis. Using these new tools, the secondary structure of the HIV-1 5 ′ untranslated region (5 ′ UTR) was determined using selective 2 ′ -hydroxyl acylation analyzed by primer extension (SHAPE), matching the results of previous work.

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Multiple conformational states of riboswitches fine-tune gene regulation

Cited by 58 publications

References 57 publications

Ligand-mediated and tertiary interactions cooperatively stabilize the P1 region in the guanine-sensing riboswitch

Ligand-mediated and tertiary interactions cooperatively stabilize the P1 region in the guanine-sensing riboswitch

Proteins That Chaperone RNA Regulation

RiboCAT: a new capillary electrophoresis data analysis tool for nucleic acid probing

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