Unique quadruplex structures of d(GGA)4 (12-mer) and d(GGA)8 (24-mer)--Direct evidence of the formation of non-canonical base pairs and structural comparison--

Matsugami, Akimasa; Ouhashi, Kiyoshi; Ikeda, Tetsuro; Okuizumi, Tomoyuki; Sotoya, Hidetsugu; Uesugi, Seiichi; Katahira, Masato

doi:10.1093/nass/2.1.49

Cited by 3 publications

(4 citation statements)

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“…The DNA (34 -36) and RNA (37,38) (34,36). The same structure was formed by d(GGA) 8 (35). Similarly, but not identically, the r(GGA) 4 intramolecular parallel quadruplex is formed by one G:G:G:G tetrad plane and one G(:A):G:G(:A):G hexad plane (38).…”

Section: Discussionmentioning

confidence: 90%

Structural Diversity of Triplet Repeat RNAs

Sobczak

Michlewski

Mezer

et al. 2010

Journal of Biological Chemistry

116

153

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Tandem repeats of various trinucleotide motifs are present in the human transcriptome, but the functions of these regular sequences, which likely depend on the structures they form, are still poorly understood. To gain new insight into the structural and functional properties of triplet repeats in RNA, we have performed a biochemical structural analysis of the complete set of triplet repeat transcripts, each composed of a single sequence repeated 17 times. We show that these transcripts fall into four structural classes. The repeated CAA, UUG, AAG, CUU, CCU, CCA, and UAA motifs did not form any higher order structure under any analyzed conditions. The CAU, CUA, UUA, AUG, and UAG repeats are ordered according to their increasing tendency to form semistable hairpins. The repeated CGA, CGU, and all CNG motifs form fairly stable hairpins, whereas AGG and UGG repeats fold into stable G-quadruplexes. The triplet repeats that formed the most stable structures were characterized further by biophysical methods. UV-monitored structure melting revealed that CGG and CCG repeats form, respectively, the most and least stable hairpins of all CNG repeats. Circular dichroism spectra showed that the AGG and UGG repeat quadruplexes are formed by parallel RNA strands. Furthermore, we demonstrated that the different susceptibility of various triplet repeat transcripts to serum nucleases can be explained by the sequence and structural features of the tested RNAs. The results of this study provide a comprehensive structural foundation for the functional analysis of triplet repeats in transcripts.Trinucleotide repeats (TNRs) 4 belong to a family of microsatellite sequences also known as short tandem repeats or simple sequence repeats. TNRs are present in both prokaryotic and eukaryotic genomes and, similar to other microsatellites, show high mutation rates resulting in frequent length variability. Polymorphic TNRs are better tolerated than dinucleotide and tetranucleotide repeats in translated sequences because their length variation does not change the open reading frame.A recent survey of the human genome reference sequence showed that it harbors more than 32,000 tracts of uninterrupted TNR sequences composed of six or more repeated units. In annotated human exons, which account for less than 3% of the genomic sequence, there are as many as 1,030 TNR tracts (61). Some AT-rich TNR types, such as CTT, AAC, and AAT, are particularly underrepresented in exons, whereas GC-rich repeats (CGG, CAG, and CCG) are highly overrepresented, implying that these sequences have a functional significance. The AT-rich and GC-rich TNRs tend to localize preferentially in the 3Ј-UTR and 5Ј-UTR, respectively (1). About 60% of exonic TNRs are localized in the open reading frame. These coding repeats are primarily translated to the poly-Gln, polyAla, poly-Glu, and poly-Leu tracts. However, the amino acid coding property of TNRs is not the only feature for which these sequences are selected in exons. The other properties of TNR sequences that manifest thems...

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Section: Discussionmentioning

confidence: 90%

Structural Diversity of Triplet Repeat RNAs

Sobczak

Michlewski

Mezer

et al. 2010

Journal of Biological Chemistry

116

153

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“…This T:H:H:T G-quadruplex can be derived intramolecularlly from a (GGA) 8 ODN and was shown to be very stable, producing a melting temperature of 86°C (22). In this structure, the two T:H G-quadruplex-forming core sequences, GGAGGAGGAGG, are linked by a single adenine nucleotide that does not form any hydrogen bonds to stabilize the T:H:H:T higher order structure (Figure 1B, right , modified from reference 21) (21,22). …”

Section: Resultsmentioning

confidence: 99%

“…This unique G-quadruplex was the first identified G-quadruplex structure with pseudo-double chain reversal loops in which the loop base (A) is part of the heptad. DNA sequences with two adjacent (GGA) 4 units, (GGA) 8 , can form a very stable ( T m = 86°C) higher ordered structure by intramolecularly stacking two T:H G-quadruplexes on the heptad plane, resulting in a tetrad:heptad:heptad:tetrad (T:H:H:T) DNA structure (Figure 1B) (21,22). These structures form in the presence of physiologic concentrations of potassium ions and at neutral pH.…”

Section: Introductionmentioning

confidence: 99%

A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity

Palumbo

Memmott

Uribe

et al. 2008

Nucleic Acids Research

169

178

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The c-myb promoter contains multiple GGA repeats beginning 17 bp downstream of the transcription initiation site. GGA repeats have been previously shown to form unusual DNA structures in solution. Results from chemical footprinting, circular dichroism and RNA and DNA polymerase arrest assays on oligonucleotides representing the GGA repeat region of the c-myb promoter demonstrate that the element is able to form tetrad:heptad:heptad:tetrad (T:H:H:T) G-quadruplex structures by stacking two tetrad:heptad G-quadruplexes formed by two of the three (GGA)4 repeats. Deletion of one or two (GGA)4 motifs destabilizes this secondary structure and increases c-myb promoter activity, indicating that the G-quadruplexes formed in the c-myb GGA repeat region may act as a negative regulator of the c-myb promoter. Complete deletion of the c-myb GGA repeat region abolishes c-myb promoter activity, indicating dual roles of the c-myb GGA repeat element as both a transcriptional repressor and an activator. Furthermore, we demonstrated that Myc-associated zinc finger protein (MAZ) represses c-myb promoter activity and binds to the c-myb T:H:H:T G-quadruplexes. Our findings show that the T:H:H:T G-quadruplex-forming region in the c-myb promoter is a critical cis-acting element and may repress c-myb promoter activity through MAZ interaction with G-quadruplexes in the c-myb promoter.

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“…It should be noted that the solution conditions (100 mM NaCl) under which the CD spectrum of this G-quadruplex-forming oligonucleotide was collected were the same as those used by Wang and Patel in their original NMR spectroscopic study of the Tetrahymena telomeric DNA . Also included in Figure are the CD spectra of the two other known G-quadruplex solution structures that were solved using NMR spectroscopy, namely the parallel heptad−tetrad G-quadruplex formed in K + by the d[GGA] 8 oligonucleotide (orange line) and the antiparallel basket-type G-quadruplex formed in Na + by the d[T 2 AG 3 ] 4 oligonucleotide (blue line) (the NMR study in this case was of a 3.5-copy of the human telomeric repeating motifs 15c ). In our comparison of the four oligonucleotides formed by G-quadruplexes, similar concentrations (∼12.5 μM in each case) and standard equilibration conditions of 1 day at room temperature were used prior to analysis.…”

Section: Resultsmentioning

confidence: 99%

Telomestatin and Diseleno Sapphyrin Bind Selectively to Two Different Forms of the Human Telomeric G-Quadruplex Structure

et al. 2005

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The human telomeric sequence d[T(2)AG(3)](4) has been demonstrated to form different types of G-quadruplex structures, depending upon the incubation conditions. For example, in sodium (Na(+)), a basket-type G-quadruplex structure is formed. In this investigation, using circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-quadruplex-binding ligands affects the conformation of the telomeric G-quadruplex found in solution. The results show that while telomestatin binds preferentially to the basket-type G-quadruplex structure with a 2:1 stoichiometry, 5,10,15,20-[tetra-(N-methyl-3-pyridyl)]-26-28-diselena sapphyrin chloride (Se2SAP) binds to a different form with a 1:1 stoichiometry in potassium (K(+)). CD studies suggest that Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce the formation of the basket-type G-quadruplex from a random coil human telomeric oligonucleotide, even in the absence of added monovalent cations such as K(+) or Na(+). In contrast, in the presence of K(+), Se2SAP was found to convert the preformed basket G-quadruplex to the hybrid structure. The significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.

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Unique quadruplex structures of d(GGA)4 (12-mer) and d(GGA)8 (24-mer)--Direct evidence of the formation of non-canonical base pairs and structural comparison--

Cited by 3 publications

References 0 publications

Structural Diversity of Triplet Repeat RNAs

Structural Diversity of Triplet Repeat RNAs

A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity

Telomestatin and Diseleno Sapphyrin Bind Selectively to Two Different Forms of the Human Telomeric G-Quadruplex Structure

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