Crystal Structure of an RNA Quadruplex Containing Inosine Tetrad: Implications for the Roles of NH2 Group in Purine Tetrads

Pan, Baocheng; Shi, Ke; Sundaralingam, M.

doi:10.1016/j.jmb.2006.08.022

Cited by 39 publications

(26 citation statements)

References 35 publications

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“…Addition of Sr 2+ improved the diffraction limit of those crystals (Mueller et al, 1999) from 1.7 Å to 1.16 Å. The specific binding of Sr 2+ to RNA 3′ cis -diols is further exemplified by the crystal structure of a quadruplex-forming RNA (Figure 4C; Pan et al, 2006). Besides at RNA 3′ termini, we observe Sr 2+ frequently making bidentate innersphere interactions with the Hoogsteen faces of purines, at bulges and junctions where phosphates cluster, or bridging across the narrow major groove (Figure S1).…”

Section: Resultsmentioning

confidence: 90%

Dramatic Improvement of Crystals of Large RNAs by Cation Replacement and Dehydration

Zhang

Ferré-D′Amaré

2014

Structure

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Summary Compared to globular proteins, RNAs with complex three-dimensional folds are characterized by poorly differentiated molecular surfaces dominated by backbone phosphates, sparse tertiary contacts stabilizing global architecture, and conformational flexibility. The resulting generally poor order of crystals of large RNAs and their complexes frequently hampers crystallographic structure determination. We describe and rationalize a post-crystallization treatment strategy that exploits the importance of solvation and counterions for RNA folding. Replacement of Li+ and Mg2+ needed for growth of crystals of a tRNA-riboswitch-protein co-crystal with Sr2+, coupled with dehydration, dramatically improved the resolution limit (8.5 to 3.2 Å) and data quality, enabling structure determination. The soft Sr2+ ion forms numerous stabilizing intermolecular contacts. Comparison of pre- and post-treatment structures reveals how RNA assemblies redistribute as quasi-rigid bodies to yield improved crystal packing. Cation exchange complements previously reported post-crystallization dehydration of protein crystals, and represents a potentially general strategy for improving crystals of large RNAs.

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Section: Resultsmentioning

confidence: 90%

Dramatic Improvement of Crystals of Large RNAs by Cation Replacement and Dehydration

Zhang

Ferré-D′Amaré

2014

Structure

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“…The authors noted ‘This complex is so stable that it would be surprising if similar structures do not occur in nature’. Based on 2D NMR spectra and molecular dynamics data, the UG 4 U sequence motif was further proposed to form a parallel-stranded tetraplex structure containing four stacked G-quartets and at least one U-quartet (31,32). Other early studies linked formation of RNA G-quadruplex structures to biological events in viruses, such HIV or herpes simplex virus (33,34), and four-stranded RNA structures formed from G-rich sequences were proposed to be involved in the processing and translational control in human transcripts (35–43).…”

Section: Introductionmentioning

confidence: 99%

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

Bugaut

Balasubramanian

2012

Nucleic Acids Research

561

512

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RNA structures in the untranslated regions (UTRs) of mRNAs influence post-transcriptional regulation of gene expression. Much of the knowledge in this area depends on canonical double-stranded RNA elements. There has been considerable recent advancement of our understanding of guanine(G)-rich nucleic acids sequences that form four-stranded structures, called G-quadruplexes. While much of the research has been focused on DNA G-quadruplexes, there has recently been a rapid emergence of interest in RNA G-quadruplexes, particularly in the 5′-UTRs of mRNAs. Collectively, these studies suggest that RNA G-quadruplexes exist in the 5′-UTRs of many genes, including genes of clinical interest, and that such structural elements can influence translation. This review features the progresses in the study of 5′-UTR RNA G-quadruplex-mediated translational control. It covers computational analysis, cell-free, cell-based and chemical biology studies that have sought to elucidate the roles of RNA G-quadruplexes in both cap-dependent and -independent regulation of mRNA translation. We also discuss protein trans-acting factors that have been implicated and the evidence that such RNA motifs have potential as small molecule target. Finally, we close the review with a perspective on the future challenges in the field of 5′-UTR RNA G-quadruplex-mediated translation regulation.

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“…[4][5][6] So far, several modifications have been suggested in the guanine motif, and the formed quadruplex structures have been experimentally examined. 7,8 Other purines (adenine, [9][10][11][12] hypoxanthine 8,[13][14][15][16] ) and pyrimidines (uracil, [17][18][19] thymine, 20 cytosine [21][22][23] ) have also been investigated experimentally and computationally as building blocks of quadruplex structures. In all of these cases, the neighboring heterocycles are connected by only one H-bond in the tetrad structures, causing a weaker interaction and a less planar geometry than in guanine tetrads.…”

Section: Introductionmentioning

confidence: 99%

3-Substituted xanthines as promising candidates for quadruplex formation: computational, synthetic and analytical studies

et al. 2011

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Our computational studies suggest that 3-substituted xanthines are good candidates for tetrad and quadruplex structures. 3-Methylxanthine (3MX) has been synthesized from 7-benzylxanthine, and the existence of tetrameric and octameric aggregates of 3MX with NH 4 + , Na + and K + ions in the gas phase (MS) and in DMSO-d 6 solution (NMR) has been observed. The ''internal'' H-bonds (N1HÁ Á ÁO6) are stronger than the ''external'' ones (N7HÁ Á ÁO2) in these clusters (NMR). Fig. 1 Tetrads composed of 7H-3-methylxanthine (3MX) and different cations [cat + = none, Na + , K + , NH 4 + ; purine atom and spectroscopic (underlined) numbering shown in upper left ring].

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Crystal Structure of an RNA Quadruplex Containing Inosine Tetrad: Implications for the Roles of NH2 Group in Purine Tetrads

Cited by 39 publications

References 35 publications

Dramatic Improvement of Crystals of Large RNAs by Cation Replacement and Dehydration

Dramatic Improvement of Crystals of Large RNAs by Cation Replacement and Dehydration

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

3-Substituted xanthines as promising candidates for quadruplex formation: computational, synthetic and analytical studies

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