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The ability of G-rich single stranded nucleic acid molecules to form three-dimensional quadruplex structures is well documented (1,2,3) . The G-quadruplex structure, also known as G-quartet, is composed of stacked G-tetrads, which are square co-planar arrays of four guanine bases each. These interesting structures may be formed by repeated folding of a single nucleic acid molecule or by interaction of two or four strands and are generally very stable due to cyclic Hoogsteen hydrogen bonding between the four guanines within each tetrad.

G-quadruplex drawing


Predicted intramolecular G-quadruplex
formed by a ‘G’-Rich Sequence (GRS)
found near alternatively spliced site of
cardiac isoform SLC4a3 mouse

Naturally occurring G-quadruplex sequence motifs have been reported in telomeric, promoters and other regions of mammalian genomes. ‘G’ rich sequences (GRS) capable of forming G-quadruplexes, have also been implicated in a variety of biological activities such as: mRNA stability (3), transcription pausing (4) , FMRP binding (5) , translation initiation (6) as well as repression (7).

We have previously shown that a conserved ‘G’ rich sequence found in the polyadenylation regions of human genes can mediate efficient 3’end processing of mammalian pre-mRNAs (8,9) , by interacting with DSEF1/hnRNP H’ protein (10) .

Formation of Cleavage-Polyadenylation complex on mammalian pre-mRNA undergoing 3' end RNA processing

Our preliminary analysis has also revealed the presence of G-rich quadruplex forming sequences near splice junctions of several human transcripts (11) . Members of the hnRNP H protein subfamily, that bind ‘G’ rich motifs, are known to be involved in alternative and tissue specific regulated splicing events (12,13,14) . We believe that G-quadruplexes play a role in modulating the differential RNA processing events by interacting with hnRNP H subfamily of RNA binding proteins.

In order to investigate the role of Quadruplex forming G-Rich Sequences (QGRS) in regulated RNA processing, we have created a suite of computational tools to map putative G-quadruplex elements within mammalian genes. The suite contains algorithms (11) to search genes for occurrences of the G-quadruplex motif and analyze their distribution patterns near RNA processing sites.


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12 Min, H., Chan, R.C. and Black, D.L. (1995).Genes Dev., 9: 2659-2671.
12 M.-Y. Chou, N. Rooke, C.W. Turck, and D.L Black. Mol. Cell. Biol. 19: 69-77. 1999.
14 M. Caputi, and A.M. Zahler. EMBO J. 21: 845-855, 2002.
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