scholarly journals A Toolbox for Predicting G-Quadruplex Formation and Stability

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Han Min Wong ◽  
Oliver Stegle ◽  
Simon Rodgers ◽  
Julian Leon Huppert
Keyword(s):  
Data Sources ◽  
Monovalent Cations ◽  
Exciting Field ◽  
Physiological Conditions ◽  
Predictive Algorithm ◽  
G Quadruplex ◽  
Wide Availability ◽  
Quadruplex Formation ◽  
Nucleic Acid Structures ◽  
Computational Predictions

G-quadruplexes are four stranded nucleic acid structures formed around a core of guanines, arranged in squares with mutual hydrogen bonding. Many of these structures are highly thermally stable, especially in the presence of monovalent cations, such as those found under physiological conditions. Understanding of their physiological roles is expanding rapidly, and they have been implicated in regulating gene transcription and translation among other functions. We have built a community-focused website to act as a repository for the information that is now being developed. At its core, this site has a detailed database (QuadDB) of predicted G-quadruplexes in the human and other genomes, together with the predictive algorithm used to identify them. We also provide a QuadPredict server, which predicts thermal stability and acts as a repository for experimental data from all researchers. There are also a number of other data sources with computational predictions. We anticipate that the wide availability of this information will be of use both to researchers already active in this exciting field and to those who wish to investigate a particular gene hypothesis.

scholarly journals A novel G-quadruplex motif in the Human MET promoter region

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Jing Yan ◽  
Deming Zhao ◽  
Liping Dong ◽  
Shuang Pan ◽  
Fengjin Hao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Luciferase Assay ◽  
Klenow Fragment ◽  
Regulate Gene Expression ◽  
Physiological Conditions ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Quadruplex Formation

It is known that the guanine-rich strands in proto-oncogene promoters can fold into G-quadruplex structures to regulate gene expression. An intramolecular parallel G-quadruplex has been identified in MET promoter. It acts as a repressor in regulating MET expression. However, the full guanine-rich region in MET promoter forms a hybrid parallel/antiparallel G-quadruplex structure under physiological conditions, which means there are some antiparallel and hybrid parallel/antiparallel G-quadruplex structures in this region. In the present study, our data indicate that g3-5 truncation adopts an intramolecular hybrid parallel/antiparallel G-quadruplex under physiological conditions in vitro. The g3-5 G-quadruplex structure significantly stops polymerization by Klenow fragment in K+ buffer. Furthermore, the results of circular dichroism (CD) spectra and polymerase stop assay directly demonstrate that the G-quadruplex structure in g3-5 fragment can be stabilized by the G-quadruplex ligand TMPyP4 (5,10,15,20-tetra-(N-methyl-4-pyridyl) porphine). But the dual luciferase assay indicates TMPyP4 has no effect on the formation of g3-5 G-quadruplex in HepG2 cells. The findings in the present study will enrich our understanding of the G-quadruplex formation in proto-oncogene promoters and the mechanisms of gene expression regulation.

scholarly journals G-quadruplex forming sequences in the genome of all known human viruses: a comprehensive guide

2018 ◽  
Author(s):  
Enrico Lavezzo ◽  
Michele Berselli ◽  
Ilaria Frasson ◽  
Rosalba Perrone ◽  
Giorgio Palù ◽  
...  
Keyword(s):  
Biological Activity ◽  
Viral Genome ◽  
Statistical Significance ◽  
Comprehensive Analysis ◽  
G Quadruplex ◽  
Quadruplex Formation ◽  
Genome Context ◽  
Human Viruses ◽  
Interactive Navigation ◽  
Nucleic Acid Structures

ABSTRACTG-quadruplexes are non-canonical nucleic acid structures that control transcription, replication, and recombination in organisms. G-quadruplexes are present in eukaryotes, prokaryotes, and viruses. In the latter, mounting evidence indicates their key biological activity. Since data on viruses are scattered, we here present a comprehensive analysis of putative G-quadruplexes in the genome of all known viruses that can infect humans. We show that the presence, distribution, and location of G-quadruplexes are features characteristic of each virus class and family. Our statistical analysis proves that their presence within the viral genome is orderly arranged, as indicated by the possibility to correctly assign up to two-thirds of viruses to their exact class based on the G-quadruplex classification. For each virus we provide: i) the list of all G-quadruplexes formed by GG-, GGG- and GGGG-islands present in the genome (positive and negative strands), ii) their position in the viral genome along with the known function of that region, iii) the degree of conservation among strains of each G-quadruplex in its genome context, iv) the statistical significance of G-quadruplex formation. This information is accessible from a database (http://www.medcomp.medicina.unipd.it/main_site/doku.php?id=g4virus) to allow the easy and interactive navigation of the results. The availability of these data will greatly expedite research on G-quadruplex in viruses, with the possibility to accelerate finding therapeutic opportunities to numerous and some fearsome human diseases.

scholarly journals DNA polymerase δ stalls on telomeric lagging strand templates independently from G-quadruplex formation

2013 ◽  
Vol 41 (22) ◽  
pp. 10323-10333 ◽  
Author(s):  
Justin D. Lormand ◽  
Noah Buncher ◽  
Connor T. Murphy ◽  
Parminder Kaur ◽  
Marietta Y. Lee ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Dna Polymerase Δ ◽  
G Quadruplex ◽  
Quadruplex Formation ◽  
Lagging Strand

The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke
Keyword(s):  
Current Knowledge ◽  
Future Research ◽  
Transcriptional Level ◽  
Cellular Functions ◽  
Multiple Functions ◽  
Open Questions ◽  
G Quadruplex ◽  
Cellular Pathways ◽  
Nucleic Acid Structures ◽  
Dependent Processes

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

scholarly journals Overlapping but distinct: a new model for G-quadruplex biochemical specificity

2021 ◽  
Author(s):  
Martin Volek ◽  
Sofia Kolesnikova ◽  
Katerina Svehlova ◽  
Pavel Srb ◽  
Ráchel Sgallová ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Drug Design ◽  
Solution Structure ◽  
Biochemical Data ◽  
Biological Regulation ◽  
New Model ◽  
G Quadruplex ◽  
Range Of Functions ◽  
Nucleic Acid Structures ◽  
Sequence Requirements

Abstract G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads. They are capable of a range of functions and thought to play widespread biological roles. This diversity raises an important question: what determines the biochemical specificity of G-quadruplex structures? The answer is particularly important from the perspective of biological regulation because genomes can contain hundreds of thousands of G-quadruplexes with a range of functions. Here we analyze the specificity of each sequence in a 496-member library of variants of a reference G-quadruplex with respect to five functions. Our analysis shows that the sequence requirements of G-quadruplexes with these functions are different from one another, with some mutations altering biochemical specificity by orders of magnitude. Mutations in tetrads have larger effects than mutations in loops, and changes in specificity are correlated with changes in multimeric state. To complement our biochemical data we determined the solution structure of a monomeric G-quadruplex from the library. The stacked and accessible tetrads rationalize why monomers tend to promote a model peroxidase reaction and generate fluorescence. Our experiments support a model in which the sequence requirements of G-quadruplexes with different functions are overlapping but distinct. This has implications for biological regulation, bioinformatics, and drug design.

scholarly journals TGF‐β‐induced fibrotic stress increases G‐quadruplex formation in human fibroblasts

FEBS Letters ◽  
2019 ◽  
Vol 593 (22) ◽  
pp. 3149-3161 ◽  
Author(s):  
Priyanka Toshniwal ◽  
Michelle Nguyen ◽  
Aurore Guédin ◽  
Helena Viola ◽  
Diwei Ho ◽  
...  
Keyword(s):  
Human Fibroblasts ◽  
G Quadruplex ◽  
Quadruplex Formation

Inhibition of Protein Synthesis Through RNA-Based Tandem G-Quadruplex Formation

2021 ◽  
Author(s):  
Masaki Hagihara
Keyword(s):  
Protein Synthesis ◽  
Reverse Transcriptase ◽  
Repeat Sequences ◽  
Guanine Quadruplex ◽  
G Quadruplex ◽  
Inhibition Of Protein Synthesis ◽  
Quadruplex Formation

Tandem guanine repeat sequences can adopt guanine quadruplex (G-quadruplex) structures and consecutive guanine repeat sequences can potentially afford multiple G-quadruplex structures. By using a reverse transcriptase stop assay and biophysical...

scholarly journals Structure and Stability of a Dimeric G-Quadruplex Formed by Cyclic Oligonucleotides

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Joan Casals ◽  
Júlia Viladoms ◽  
Enrique Pedroso ◽  
Carlos González
Keyword(s):  
Telomeric Repeat ◽  
High Melting ◽  
Structure And Stability ◽  
Dimeric Structure ◽  
Nmr Data ◽  
High Melting Temperature ◽  
Sodium Nmr ◽  
G Quadruplex ◽  
Global Topology ◽  
Quadruplex Formation

We have studied the structure and stability of the cyclic dodecamer d<pGGGTTAGGGTTA>, containing two copies of the human telomeric repeat. In the presence of sodium, NMR data are consistent with a dimeric structure of the molecule in which two cycles self-associate forming a quadruplex with three guanine tetrads connected by edgewise loops. The two macrocycles are arranged in a parallel way, and the dimeric structure exhibits a high melting temperature. These results indicate that cyclization of the phosphodiester chain does not prevent quadruplex formation, although it affects the global topology of the quadruplex.

scholarly journals Mutagenesis Reveals an Unusual Combination of Guanines in RNA G-Quadruplex Formation

ACS Omega ◽  
2017 ◽  
Vol 2 (8) ◽  
pp. 4790-4799
Author(s):  
Prachi Agarwala ◽  
Gargi Pal ◽  
Satyaprakash Pandey ◽  
Souvik Maiti
Keyword(s):  
G Quadruplex ◽  
Unusual Combination ◽  
Quadruplex Formation
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