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Open AccessJournal ArticleDOI

GRSDB: a database of quadruplex forming G-rich sequences in alternatively processed mammalian pre-mRNA sequences

TLDR
The computational approach is applied to map putative Quadruplex forming GRSs within the transcribed regions of a large number of alternatively processed human and mouse gene sequences that were obtained as fully annotated entries from GenBank and RefSeq to build the GRSDB database, which provides a unique avenue for studying G-quadruplexes in the context of RNA processing sites.
Abstract
Guanine-rich nucleic acids are known to form highly stable G-quadruplex structures, also known as G-quartets. Recently, there has been a tremendous amount of interest in studying G-quadruplexes owing to the realization of their biological importance. G-rich sequences (GRSs) capable of forming G-quadruplexes are found in the vicinity of polyadenylation regions and are involved in regulating 3' end processing of mammalian pre-mRNAs. G-rich motifs are also known to play an important role in alternative, tissue-specific splicing by interacting with hnRNP H protein subfamily. Whether quadruplex structure directly plays a role in regulating RNA processing events requires further investigation. To date there has not been a comprehensive effort to study G-quadruplexes near RNA processing sites. We have applied a computational approach to map putative Quadruplex forming GRSs within the transcribed regions of a large number of alternatively processed human and mouse gene sequences that were obtained as fully annotated entries from GenBank and RefSeq. We have used the computed data to build the GRSDB database that provides a unique avenue for studying G-quadruplexes in the context of RNA processing sites. GRSDB website offers visual comparison of G-quadruplex distribution patterns among all the alternative RNA products of a gene with the help of dynamic graphics. At present, GRSDB contains data from 1310 human and mouse genes, of which 1188 are alternatively processed. It has a total of 379 223 predicted G-quadruplexes, of which 54 252 are near RNA processing sites. GRSDB is a good resource for researchers interested in investigating the functional relevance of G-quadruplexes, especially in the context of alternative RNA processing. It can be accessed at http://bioinformatics.ramapo.edu/grsdb/.

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Citations
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Journal ArticleDOI

Quadruplex DNA: sequence, topology and structure

TL;DR: This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence.
Journal ArticleDOI

Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics

TL;DR: The review highlights recent solution NMR-based G-quadruplex structures formed by the four-repeat human telomere in K+ solution and the guanine-rich strands of c-myc, c-kit and variant bcl-2 oncogenic promoters, as well as a bimolecular G- quadruplex that targets HIV-1 integrase.
Journal ArticleDOI

QGRS Mapper: a web-based server for predicting G-quadruplexes in nucleotide sequences

TL;DR: A web-based server that predicts quadruplex forming G-rich sequences (QGRS) in nucleotide sequences and features interactive graphic representation of the data is developed, very useful for investigating the functional relevance of G-quadruplex structure, in particular its role in regulating the gene expression by alternative processing.
Journal ArticleDOI

5′-UTR RNA G-quadruplexes: translation regulation and targeting

TL;DR: This review features the progresses in the study of 5′-UTR RNA G-quadruplex-mediated translational control and discusses protein trans-acting factors that have been implicated and the evidence that such RNA motifs have potential as small molecule target.
Journal ArticleDOI

G-Quadruplexes: Targets in Anticancer Drug Design

TL;DR: A summary of published research that has set out to address the problem of selectivity of G‐quadruplexes and research methodologies that have been developed to study the binding of ligands to G‐ quadruplexes are provided.
References
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Journal ArticleDOI

Prevalence of quadruplexes in the human genome

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.
Journal ArticleDOI

Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays.

TL;DR: These genome-wide data provide experimental evidence and tissue distributions for thousands of known and novel alternative splicing events and indicate that at least 74% of human multi-exon genes are alternatively spliced.
Journal ArticleDOI

G-quartets 40 years later: from 5'-GMP to molecular biology and supramolecular chemistry.

TL;DR: This Review integrates and summarizes knowledge gained from areas ranging from structural biology and medicinal chemistry to supramolecular chemistry and nanotechnology, with emphasis on G-quartet structure, function, and molecular recognition.
Journal ArticleDOI

Helix Formation by Guanylic Acid

TL;DR: From examination of the optical properties of the gel and investigation of the structure of fibers obtained from the gel by drying, it is concluded that, at least in the case of the 5' isomer, the phenomenon may be explained as being due to helix formation by the guanylic acid.
Journal ArticleDOI

Pre-mRNA splicing and human disease

TL;DR: The purpose of this review is to highlight the different mechanisms by which disruption of pre-mRNA splicing play a role in human disease.
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