SINDH UNIVERSITY RESEARCH JOURNAL (SCIENCE SERIES) QuadLocator - An Algorithm to Locate Possible Quadruplex Forming Sequences
01 Jan 2015-
TL;DR: A new algorithm is proposed in this paper with an additional feature that can perform transcript-exon mapping for G-quadruplex structure and there is a possibility that a possible quadruplex forming sequence may found because of joining of two exons in a mature transcript but not in case of DNA or RNA.
Abstract: An unusual four stranded structure, known as G-quadruplex structure, can be formed in a DNA/RNA segment having frequent guanines. These structures can be involved in different biological processes and to understand this, it is necessary to identify the locations of those segments that can form these unusual structures. Different tools are available to locate such sequences in a given nucleic acid sequence. However, a new algorithm is proposed in this paper with an additional feature that can perform transcript-exon mapping for these structures. It is important because there is a possibility that a possible quadruplex forming sequence may found because of joining of two exons in a mature transcript but not in case of DNA or RNA.
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TL;DR: The principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization is established, establishing the principle that the purine-rich strand of the DNA in this region can form two different intramolecular G- quadruplex structures.
Abstract: The nuclease hypersensitivity element III1 upstream of the P1 promoter of c-MYC controls 85–90% of the transcriptional activation of this gene. We have demonstrated that the purine-rich strand of the DNA in this region can form two different intramolecular G-quadruplex structures, only one of which seems to be biologically relevant. This biologically relevant structure is the kinetically favored chair-form G-quadruplex, which is destabilized when mutated with a single G → A transition, resulting in a 3-fold increase in basal transcriptional activity of the c-MYC promoter. The cationic porphyrin TMPyP4, which has been shown to stabilize this G-quadruplex structure, is able to suppress further c-MYC transcriptional activation. These results provide compelling evidence that a specific G-quadruplex structure formed in the c-MYC promoter region functions as a transcriptional repressor element. Furthermore, we establish the principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization.
1,969 citations
TL;DR: There is a significant repression of quadruplexes in the coding strand of exonic regions, which suggests that quadruplex-forming patterns are disfavoured in sequences that will form RNA.
Abstract: Guanine-rich DNA sequences of a particular form have the ability to fold into four-stranded structures called G-quadruplexes. In this paper, we present a working rule to predict which primary sequences can form this structure, and describe a search algorithm to identify such sequences in genomic DNA. We count the number of quadruplexes found in the human genome and compare that with the figure predicted by modelling DNA as a Bernoulli stream or as a Markov chain, using windows of various sizes. We demonstrate that the distribution of loop lengths is significantly different from what would be expected in a random case, providing an indication of the number of potentially relevant quadruplex-forming sequences. In particular, we show that there is a significant repression of quadruplexes in the coding strand of exonic regions, which suggests that quadruplex-forming patterns are disfavoured in sequences that will form RNA.
1,493 citations
TL;DR: Folding of telomeric DNA into G-quartet structures seems to influence the extent of telomere elongation in vitro and might therefore act as a negative regulator of lengthening in vivo.
Abstract: The ends or telomeres of the linear chromosomes of eukaryotes are composed of tandem repeats of short DNA sequences, one strand being rich in guanine (G strand) and the complementary strand in cytosine. Telomere synthesis involves the addition of telomeric repeats to the G strand by telomere terminal transferase (telomerase). Telomeric G-strand DNAs from a variety of organisms adopt compact structures, the most stable of which is explained by the formation of G-quartets. Here we investigate the capacity of the different folded forms of telomeric DNA to serve as primers for the Oxytricha nova telomerase in vitro. Formation of the K(+)-stabilized G-quartet structure in a primer inhibits its use by telomerase. Furthermore, the octanucleotide T4G4, which does not fold, is a better primer than (T4G4)2, which can form a foldback structure. We conclude that telomerase does not require any folding of its DNA primer. Folding of telomeric DNA into G-quartet structures seems to influence the extent of telomere elongation in vitro and might therefore act as a negative regulator of elongation in vivo.
1,094 citations
TL;DR: RNA selection is used to demonstrate that G quartets serve as physiologically relevant targets for FMRP and identify mRNAs whose dysregulation may underlie human mental retardation.
918 citations
TL;DR: The G-Quartet in Supramolecular Chemistry and Nanoscience and the Biology of G-Rich Genomic Regions examines the role of cations in determining Quadruplex structure and stability.
Abstract: Fundamentals of Quadruplex Structures Stephen Neidle and Shankar Balasubramanian Energetics, Kinetics and Dynamics of Quadruplex Folding Structural Diversity of G-Quadruplex Scaffolds The Role of Cations in Determining Quadruplex Structure and Stability DNA Quadruplex-Ligand Recognition: Structure and Dynamics Quadruplex Ligand Recognition: Biological Aspects Quadruplexes and Gene Regulation Quadruplexes in the Genome Quadruplexes and the Biology of G-Rich Genomic Regions The G-Quartet in Supramolecular Chemistry and Nanoscience
443 citations