RNA structural motifs: building blocks of a modular biomolecule

Hendrix, Donna K.; Brenner, Steven E.; Holbrook, Stephen R.

doi:10.1017/s0033583506004215

Cited by 196 publications

(143 citation statements)

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“…There is a growing interest in characterizing both the nature and dynamics of these changes, which have important implications for the consequences and regulation of these binding events. This is particularly relevant for RNA-protein interactions, since RNA molecules can exhibit a diverse array of structural features under physiological conditions [1,2]. Fluorescence-based approaches offer a powerful approach to monitor macromolecular conformational changes in solution; however, the intrinsic fluorescence of nucleic acid bases is too weak to assess nucleic acid conformational events directly.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence intensity decays of 2-aminopurine solutions: Lifetime distribution approach

Bharill

Sarkar

Ballin

et al. 2008

Analytical Biochemistry

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The fluorescent adenine analogue 2-aminopurine (2AP) has been used extensively to monitor conformational changes and macromolecular binding events involving nucleic acids because its fluorescence properties are highly sensitive to changes in chemical environment. Furthermore, site-specific incorporation of 2AP permits local DNA and RNA conformational events to be discriminated from the global structural changes monitored by UV/Vis spectroscopy and circular dichroism. However, while the steady-state fluorescence properties of 2AP have been well defined in diverse settings, interpretation of 2AP fluorescence lifetime parameters has been hampered by the heterogeneous nature of multi-exponential 2AP intensity decays observed across populations of microenvironments. To resolve this problem, we have tested the utility of multi-exponential versus continuous Lorentzian lifetime distribution models to describe fluorescence intensity decays from 2AP in diverse chemical backgrounds and within the context of RNA. Heterogeneity was introduced into 2AP intensity decays by mixing solvents of differing polarities, or by adding quenchers under high viscosity to evaluate the transient effect. Heterogeneity of 2AP fluorescence within the context of a synthetic RNA hairpin was introduced by structural remodeling using a magnesium salt. In each case, except folded RNA which required a bimodal distribution, 2AP lifetime properties were well described by single Lorentzian distribution functions, abrogating the need to introduce additional discrete lifetime subpopulations. Rather, heterogeneity in fluorescence decay processes was accommodated by the breadth of each distribution. This approach also permitted solvent relaxation effects on 2AP emission to be assessed by comparing lifetime distributions at multiple wavelengths. Together, these studies provide a new perspective for the interpretation of 2AP fluorescence lifetime properties, which will further the utility of this Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript fluorophore in analyses of the complex and heterogeneous structural microenvironments associated with nucleic acids.

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Section: Introductionmentioning

confidence: 99%

Fluorescence intensity decays of 2-aminopurine solutions: Lifetime distribution approach

Bharill

Sarkar

Ballin

et al. 2008

Analytical Biochemistry

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“…[54][55][56] Secondary structure motifs fall into four classes ( Figure 3): (i) stacks, (ii) loops, (iii) joints, and (iv) free ends. In essence, the stacks provide the (only) stabilizing contributions to RNA structure, whereas the other elements are accompanied with positive free energy contributions.…”

Section: Nucleic Acid Structuresmentioning

confidence: 99%

Genotypes and Phenotypes in the Evolution of Molecules

Schuster

2009

European Review

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“…These subcomponents can be found in different locations or even different RNA structures. The so-called RNA structural motifs, or the "building blocks" of the RNA architecture (Moore 1999;Hendrix et al 2005; Leontis et al 2006), are highly modulated components with conserved 3D geometries and molecular functions. These features make them critically important in analyzing RNA 3D structures in a well-organized manner.…”

Section: Introductionmentioning

confidence: 99%

RNAMotifScanX: a graph alignment approach for RNA structural motif identification

Zhong

Zhang

2015

RNA

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RNA structural motifs are recurrent three-dimensional (3D) components found in the RNA architecture. These RNA structural motifs play important structural or functional roles and usually exhibit highly conserved 3D geometries and base-interaction patterns. Analysis of the RNA 3D structures and elucidation of their molecular functions heavily rely on efficient and accurate identification of these motifs. However, efficient RNA structural motif search tools are lacking due to the high complexity of these motifs. In this work, we present RNAMotifScanX, a motif search tool based on a base-interaction graph alignment algorithm. This novel algorithm enables automatic identification of both partially and fully matched motif instances. RNAMotifScanX considers noncanonical base-pairing interactions, base-stacking interactions, and sequence conservation of the motifs, which leads to significantly improved sensitivity and specificity as compared with other state-of-the-art search tools. RNAMotifScanX also adopts a carefully designed branch-and-bound technique, which enables ultra-fast search of large kink-turn motifs against a 23S rRNA. The software package RNAMotifScanX is implemented using GNU C++, and is freely available from http://genome.ucf.edu/RNAMotifScanX.

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RNA structural motifs: building blocks of a modular biomolecule

Cited by 196 publications

References 131 publications

Fluorescence intensity decays of 2-aminopurine solutions: Lifetime distribution approach

Fluorescence intensity decays of 2-aminopurine solutions: Lifetime distribution approach

Genotypes and Phenotypes in the Evolution of Molecules

RNAMotifScanX: a graph alignment approach for RNA structural motif identification

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