G-Quadruplexes: Prediction, Characterization, and Biological Application

Kwok, Chun Kit; Merrick, Catherine J.

doi:10.1016/j.tibtech.2017.06.012

Cited by 322 publications

(262 citation statements)

References 142 publications

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“…For example, surplus G-tracts have been suggested to play roles in oxidative stress [133][134][135], and could (via G-register exchange) act as compensatory G-quadruplexes to circumvent (tumorigenic) G-quadruplex-destabilizing mutations. In addition, a higher number of 'GGG'-tracts [4][5][6] were shown to enhance the translational suppressor effect of artificial G-quadruplex sequences located in the 5 0 -UTR of luciferase reporter gene [136]. Thermodynamic measurements revealed a correlation between Gquadruplex thermodynamic stability and their effect on gene expression [136].…”

Section: G-tetrads: Canonical and Noncanonicalmentioning

confidence: 99%

The diverse structural landscape of quadruplexes

et al. 2019

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G‐quadruplexes are secondary structures formed in G‐rich sequences in DNA and RNA. Considerable research over the past three decades has led to in‐depth insight into these unusual structures in DNA. Since the more recent exploration into RNA G‐quadruplexes, such structures have demonstrated their in cellulo existence, function and roles in pathology. In comparison to Watson‐Crick‐based secondary structures, most G‐quadruplexes display highly redundant structural characteristics. However, numerous reports of G‐quadruplex motifs/structures with unique features (e.g. bulges, long loops, vacancy) have recently surfaced, expanding the repertoire of G‐quadruplex scaffolds. This review addresses G‐quadruplex formation and structure, including recent reports of non‐canonical G‐quadruplex structures. Improved methods of detection will likely further expand this collection of novel structures and ultimately change the face of quadruplex‐RNA targeting as a therapeutic strategy.

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Section: G-tetrads: Canonical and Noncanonicalmentioning

confidence: 99%

The diverse structural landscape of quadruplexes

et al. 2019

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“…A growing body of structural and biophysical data demonstrates that these structures frequently escape the consensus motif (i.e., G n ‐N i ‐G n ‐N j ‐G n ‐N k ‐G n , in which n= 2 to 4; i , j , k =1 to 7; and N=any base), as evidenced by snap‐back, G‐vacant, and bulged G4 structures which are difficult to predict by bioinformatics algorithms . In this context, experimental probing of formation and topology of G4 structures, both in vitro and in the cellular environment, is crucial for understanding of their persistence and biological roles, as well as for improvement of bioinformatics algorithms …”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14] In this context, experimental probing of formationa nd topology of G4 structures,b othi nv itro and in the cellular environment, is crucial for understanding of their persistence and biological roles, as well as for improvement of bioinformatics algorithms. [15][16][17][18] Along these lines, apromising approach to assess the formation and topology of G4 structures relies on the use of smallmolecule fluorescent "light-up" probes, the emissiono fw hich is triggered by interaction with the substrate. An umber of fluorescentp robes for G4-DNA have been described to date, as summarized in several recentr eviews.…”

Section: Introductionmentioning

confidence: 99%

Topology‐Selective, Fluorescent “Light‐Up” Probes for G‐Quadruplex DNA Based on Photoinduced Electron Transfer

Xie

Reznichenko

Chaput

et al. 2018

Chemistry A European J

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Six novel probes were prepared by covalent attachment of a G4-DNA ligand (bis(quinolinium) pyridodicarboxamide; PDC) to various coumarin or pyrene fluorophores. In the absence of DNA, the fluorescence of all probes is quenched due to intramolecular photoinduced electron transfer (PET), as evidenced by photophysical and electrochemical studies, molecular modeling, and DFT calculations. All probes demonstrate similarly high thermal stabilization of various G4-DNA substrates belonging to different folding topologies, as assessed by fluorescence melting experiments; however, their fluorimetric response is strongly heterogeneous with respect to the structures of the probes and G4-DNA targets. Thus, the probes containing the 7-diethylaminocoumarin fluorophore demonstrate significant fluorescence enhancement in the presence of G4-DNA, with the strongest "light-up" response (20- to 180-fold) observed for antiparallel G4 structures as well as for hybrid G4 structures, formed by the variants of human telomeric sequence and capable of a conformation change to the antiparallel isoform. These results shed light on the influence of the linker and electronic properties of fluorophores on the efficiency of G4-DNA "light-up" probes operating via PET.

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“…Over 65,000 G-rich regions were predicted in silico to form RG4 structures in Arabidopsis based on the sequence feature of GxLnGxLnGxLnGx 6,27 . However, we detected less than 3000 135 regions by rG4-seq ( Fig.…”

Section: Features Of Arabidopsis Rg4 Formable Regionsmentioning

confidence: 99%

“…For many complex RNA structures, although their 35 folding in vitro has been well defined, the folding in vivo is poorly understood. One of such complex structures is RNA G-quadruplex (RG4), which is folded with guanine-rich (G-rich) sequences in vitro and consists of two or more layers of G-quartets involving both Hoogsteen and Watson-Crick base pairs 5,6 . RG4s can be very stable in vitro in the presence of ion cations such as potassium (K + ), therefore they are hypothesized to exist in vivo and to be involved in novel 40 functions 5 , such as post-transcriptional regulation of gene expression [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

RNA G-quadruplex structures exist and function in vivo

Yang

Cheema

Zhang

et al. 2019

Preprint

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15Guanine-rich sequences are able to form complex RNA structures termed RNA G-quadruplexes in vitro. Because of their high stability, RNA G-quadruplexes are proposed to exist in vivo and are suggested to be associated with important biological relevance. However, there is a lack of direct evidence for RNA G-quadruplex formation in living cells. Therefore, it is unclear whether any purported functions are associated with the specific sequence content or the formation of an RNA 20 G-quadruplex structure. Here, we profiled the landscape of those guanine-rich regions with the in vitro folding potential in the Arabidopsis transcriptome. We found a global enrichment of RNA G-quadruplexes with two G-quartets whereby the folding potential is strongly influenced by RNA secondary structures. Using in vitro and in vivo RNA chemical structure profiling, we determined that hundreds of RNA G-quadruplex structures are strongly folded in both Arabidopsis and rice, 25 providing direct evidence of RNA G-quadruplex formation in living eukaryotic cells. Subsequent genetic and biochemical analysis showed that RNA G-quadruplex folding was sufficient to regulate translation and modulate plant growth. Our study reveals the existence of RNA Gquadruplex in vivo, and indicates that RNA G-quadruplex structures act as important regulators of plant development and growth. 30 We thank Prof.

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G-Quadruplexes: Prediction, Characterization, and Biological Application

Cited by 322 publications

References 142 publications

The diverse structural landscape of quadruplexes

The diverse structural landscape of quadruplexes

Topology‐Selective, Fluorescent “Light‐Up” Probes for G‐Quadruplex DNA Based on Photoinduced Electron Transfer

RNA G-quadruplex structures exist and function in vivo

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