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Related Concept Videos

RNA Structure01:19

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The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
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Exploring RNA conformational space under sparse distance restraints.

William R Taylor1, Russell S Hamilton2

  • 1Computational Cell and Molecular Biology, Francis Crick Institute, London, NW1 1AT, UK.

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|March 11, 2017
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Summary
This summary is machine-generated.

Coevolution analysis can predict RNA contacts to restrict molecular flexibility. However, these predictions are too inconsistent for general RNA 3D structure prediction.

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Area of Science:

  • Structural Biology
  • Computational Biology
  • Biophysics

Background:

  • RNA molecules exhibit complex conformational freedom.
  • Predicting RNA three-dimensional (3D) structure from sequence is a significant challenge.
  • Coevolution analysis offers potential insights into RNA structural constraints.

Purpose of the Study:

  • To evaluate the effectiveness of coevolution-predicted restraints in limiting RNA conformational freedom.
  • To assess the utility of these restraints for RNA 3D structure prediction.

Main Methods:

  • Application of a small number of restraints predicted by coevolution analysis.
  • Analysis of restraint effectiveness based on contact location (e.g., stemloops, pseudoknots) and RNA size.
  • Evaluation of restraint impact on topologically simple versus complex folds.

Main Results:

  • Coevolution-predicted contacts can powerfully restrict RNA conformational freedom.
  • Restraints between distal ends of adjacent stemloops show significant restriction.
  • Multiple cross-links, particularly those involving pseudoknots, provide the strongest restraint.
  • Effectiveness is reduced in larger RNA structures (>300 bases) and complex topological folds.
  • Predicted contacts are erratic in occurrence and distribution.

Conclusions:

  • Coevolution analysis can identify powerful restraints for RNA conformational freedom.
  • The erratic nature of predicted contacts limits its general applicability for RNA 3D structure prediction.
  • Further development is needed to overcome limitations for robust structure prediction.