Unraveling the structural basis for the exceptional stability of RNA G-quadruplexes capped by a uridine tetrad at the 3′ terminus

Andrałojć, Witold; Małgowska, Magdalena; Sarzyñska, Joanna; Pasternak, Karol; Szpotkowski, Kamil; Kierzek, Ryszard; Gdaniec, Zofia

doi:10.1261/rna.068163.118

Cited by 8 publications

(12 citation statements)

References 64 publications

(60 reference statements)

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“…Two crystallographically wellordered water molecules participate in inter-nucleobase hydrogen bonding. Other non-canonical tetrads have been observed in G4s, typically positioned at dimer interfaces or forming interactions with proteins (Andralojc et al, 2019;Chen et al, 2018;Cheong and Moore, 1992;Kimura et al, 2009;Pan et al, 2003;Patel et al, 2000;Patel and Hosur, 1999). For instance, the solution structure of r(UGGUGGU) shows a tetramolecular G4 containing multiple U-tetrads.…”

Section: The Fragile-x Aptamermentioning

confidence: 99%

“…For instance, the solution structure of r(UGGUGGU) shows a tetramolecular G4 containing multiple U-tetrads. Of these, the 3' terminal U-tetrad, contributes to the thermal stability of the G4, whereas in the DNA G4 of analogous sequence, the uridines lead to a 30 °C lower Tm (Andralojc et al, 2019;Cheong and Moore, 1992). The Sc1 structure is stabilized by binding of the RGG peptide to a groove between its G4 and duplex moieties (Fig.…”

Section: The Fragile-x Aptamermentioning

confidence: 99%

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The emerging structural complexity of G-quadruplex RNAs

Banco

Ferré-D′Amaré

2021

RNA

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G-quadruplexes (G4s) are four-stranded nucleic acid structures that arise from the stacking of Gquartets, cyclic arrangements of four guanines engaged in Hoogsteen base pairing. Until recently, most RNA G4 structures were thought to conform to a sequence pattern in which guanines stacking within the G4 would also be contiguous in sequence (e.g., four successive guanine trinucleotide tracts separated by loop nucleotides). Such a sequence restriction, and the stereochemical constraints inherent to RNA (arising, in particular, from presence of the 2'-OH), dictate relatively simple RNA G4 structures. Recent crystallographic and solution NMR structure determinations of a number of in vitro selected RNA aptamers has revealed RNA G4 structures of unprecedented complexity. Structures of the Sc1 aptamer that binds an RGG peptide from the Fragile-X Mental Retardation protein, various fluorescence turn-on aptamers (Corn, Mango, and Spinach), and the spiegelmer that binds the complement protein C5a, in particular, reveal complexity hitherto unsuspected in RNA G4s, including nucleotides in syn conformation, locally inverted strand polarity, and nucleotide quartets that are not all-G. Common to these new structures, the sequences folding into G4s do not conform to the requirement that guanine stacks arise from consecutive (contiguous in sequence) nucleotides. This review highlights how emancipation from this constraint drastically expands the structural possibilities of RNA G-quadruplexes.

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Section: The Fragile-x Aptamermentioning

confidence: 99%

Section: The Fragile-x Aptamermentioning

confidence: 99%

The emerging structural complexity of G-quadruplex RNAs

Banco

Ferré-D′Amaré

2021

RNA

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“…To test the tools that analyze and visualize 2D and 3D structures, we selected two PDB-deposited RNA structures that formed G-quadruplexes: an RNA aptamer (PDB id: 2RQJ) [ 72 ] with canonical G4 topology and r(GGAGGAGGAGGA) sequence and a synthetic construct of r(UGGUGGU)4 structure (PDB id: 6GE1) [ 3 ] containing U-tetrads.…”

Section: Resultsmentioning

confidence: 99%

“…In this part of the study, we tested four tools that analyze and visualize the secondary and the tertiary structures with quadruplexes. We executed them for two quadruplex RNA structures—an RNA aptamer (PDB id: 2RQJ) [ 72 ] and a synthetic construct of r(UGGUGGU)4 structure (PDB id: 6GE1) [ 3 ]—to find out what details of the structure we can obtain and in what form, numerical and graphical, they are presented. Let us note that 2RQJ is a dimer with two unimolecular structures obtained via NMR; each comprising one G-quadruplex with two tetrads of O+ type in the ONZ classification [ 2 ].…”

Section: Resultsmentioning

confidence: 99%

How bioinformatics resources work with G4 RNAs

Miskiewicz

Sarzyñska

Szachniuk

2020

Briefings in Bioinformatics

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Quadruplexes (G4s) are of interest, which increases with the number of identified G4 structures and knowledge about their biomedical potential. These unique motifs form in many organisms, including humans, where their appearance correlates with various diseases. Scientists store and analyze quadruplexes using recently developed bioinformatic tools—many of them focused on DNA structures. With an expanding collection of G4 RNAs, we check how existing tools deal with them. We review all available bioinformatics resources dedicated to quadruplexes and examine their usefulness in G4 RNA analysis. We distinguish the following subsets of resources: databases, tools to predict putative quadruplex sequences, tools to predict secondary structure with quadruplexes and tools to analyze and visualize quadruplex structures. We share the results obtained from processing specially created RNA datasets with these tools. Contact:mszachniuk@cs.put.poznan.plSupplementary information: Supplementary data are available at Briefings in Bioinformatics online.

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“…Rational incorporation of these modifications into G4FS can be used to stabilize particular conformers. Although the presence of G-tetrads is required to form G-quadruplexes, non-canonical tetrads have also been observed in high-resolution structures or models of G4s [8,[19][20][21][22][23][24][25][26][27]. G4s are more tolerant to mutations than was previously thought.…”

Section: Introductionmentioning

confidence: 98%

Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation

et al. 2021

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In this paper, a method to discriminate between two target RNA sequences that differ by one nucleotide only is presented. The method relies on the formation of alternative structures, i.e., quadruplex–duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of DNA or RNA G-rich oligonucleotides with target sequences containing 5′–GGGCUGG–3′ or 5′–GGGCGGG–3′ fragments. Using biophysical methods, we studied the effect of oligonucleotide types (DNA, RNA), non-nucleotide modifications (aliphatic linkers or abasic), and covalently attached G4 ligand on the ability of G-rich oligonucleotides to assemble a G-quadruplex motif. We demonstrated that all examined non-nucleotide modifications could mimic the external loops in the G-quadruplex domain of QDH structures without affecting their stability. Additionally, some modifications, in particular the presence of two abasic residues in the G-rich oligonucleotide, can induce the formation of non-canonical QDH instead of the Dss structure upon hybridization to a target sequence containing the GGGCUGG motif. Our results offer new insight into the sequential requirements for the formation of G-quadruplexes and provide important data on the effects of non-nucleotide modifications on G-quadruplex formation.

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Unraveling the structural basis for the exceptional stability of RNA G-quadruplexes capped by a uridine tetrad at the 3′ terminus

Cited by 8 publications

References 64 publications

The emerging structural complexity of G-quadruplex RNAs

The emerging structural complexity of G-quadruplex RNAs

How bioinformatics resources work with G4 RNAs

Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation

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