Overview of Formation of G‐Quadruplex Structures

Sannohe, Yuta; Sugiyama, Hiroshi

doi:10.1002/0471142700.nc1702s40

Cited by 42 publications

(32 citation statements)

References 127 publications

(131 reference statements)

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“…In addition to sequence modifications, another common approach to reduce polymorphism is by changing the solution conditions. The addition of biological molecules 59 (e.g. sugar, proteins), presence of co-solvents (e.g.…”

Section: Introductionmentioning

confidence: 99%

Not all G-quadruplexes are created equally: an investigation of the structural polymorphism of the c-Myc G-quadruplex-forming sequence and its interaction with the porphyrin TMPyP4

Miller

Buscaglia

et al. 2012

Org. Biomol. Chem.

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G-quadruplexes, DNA tertiary structures highly localized to functionally important sites within the human genome, have emerged as important new drug targets. The putative G-quadruplex-forming sequence (Pu27) in the NHE-III1 promoter region of the c-Myc gene is of particular interest as stabilization of this G-quadruplex with TMPyP4 has been shown to repress c-Myc transcription. In this study, we examine the Pu27 G-quadruplex-forming sequence and its interaction with TMPyP4. We report that the Pu27 sequence exists as a heterogeneous mixture of monomeric and higher-order G-quadruplex species in vitro and that this mixture can be partially resolved by size exclusion chromatography (SEC) separation. Within this ensemble of configurations, the equilibrium can be altered by modifying the buffer composition, annealing procedure, and dialysis protocol thereby affecting the distribution of G-quadruplex species formed. TMPyP4 was found to bind preferentially to higher-order G-quadruplex species suggesting the possibility of stabilization of the junctions of the c-Myc G-quadruplex multimers by porphyrin end-stacking. We also examined four modified c-Myc sequences that have been previously reported and found a narrower distribution of quadruplex configurations compared to the parent Pu27 sequence. We could not definitively conclude whether these G-quadruplex structures were selected from the original ensemble or if they are new G-quadruplex structures. Since these sequences differ considerably from the wild-type promoter sequence, it is unclear whether their structures have any actual biological relevance. Additional studies are needed to examine how the polymorphic nature of G-quadruplexes affects the interpretation of in vitro data for c-Myc and other G-quadruplexes. The findings reported here demonstrate that experimental conditions contribute significantly to G-quadruplex formation and should be carefully considered, controlled, and reported in detail.

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Section: Introductionmentioning

confidence: 99%

Not all G-quadruplexes are created equally: an investigation of the structural polymorphism of the c-Myc G-quadruplex-forming sequence and its interaction with the porphyrin TMPyP4

Miller

Buscaglia

et al. 2012

Org. Biomol. Chem.

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“…[26] Thea ddition of the complementary sequence (nt 184-208) yielded aT mo f7 3 8 8 Cf or the duplex. [26] Combined with our RTS-HBLMPCR result here (Figure 5A), it is likely that the G4s and P1 helix coexists in full length hTERC,with G4s being more stable than the P1 helix (weak GU pairs and internal loop) under physiological conditions which have high [K + ], about 150 mm.W ec annot rule out the possibility that both structures could form simultaneously with aq uadruplex comprising aCbulge (nt [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. [24] Recent protein binding and RNAmutational studies have suggested that the RNAG4-specific helicase DHX36 is involved in the binding and unwinding of aputative RNAG4 located near the 5 end of hTERC, [27] and that the G4 may facilitate the accumulation of mature hTERC needed for telomere maintenance.…”

Section: Methodsmentioning

confidence: 99%

“…[6] G4 structures exhibit characteristic features in circular dichroism, UV-thermal melting analysis,f luorescence,a nd NMR spectroscopy. [7] Thes ynthetic or in vitro transcribed (IVT) RNAc an be subjected to in-line probing to detect the presence of RNA G4s.…”

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confidence: 99%

Targeted Detection of G‐Quadruplexes in Cellular RNAs

Kwok

Balasubramanian

2015

Angewandte Chemie

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The G-quadruplex (G4) is an on-canonical nucleic acid structure whichr egulates important cellular processes. RNAG4s have recently been shown to exist in human cells and be biologically significant. Described herein is anew approach to detect and map RNAG4s in cellular transcripts.This method exploits the specific control of RNAG4-cation and RNAG4-ligand interactions during reverse transcription, by using aselective reverse transcriptase to monitor RNAG4-mediated reverse transcriptase stalling (RTS) events.Importantly,aligation-amplification strategy is coupled with RTS, and enables detection and mapping of G4s in important, low-abundance cellular RNAs.S trong evidence is provided for G4 formation in full-length cellular human telomerase RNA, offering important insights into its cellular function.

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“…3.6 G-tetraduplex and genetic instability G-quadruplexes are higher-order DNA or RNA structures formed from G-rich DNA or RNA sequences that are built around tetrads of hydrogen-bonded guanine bases (Lipps & Rhodes, 2009;Sannohe & Sugiyama, 2010). Despite the wide prevalence of genomic sequences that have G-rich property and that can potentially fold into tetraplex / quadruplexes structures, a direct demonstration of their existence in vivo proved to be a difficult undertaking.…”

Section: H-dna and H-dna Induced Dsbs And Genetic Instabilitymentioning

confidence: 99%