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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

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Evolutionary evidence for alternative structure in RNA sequence co-variation.

Justin Ritz¹, Joshua S Martin, Alain Laederach

¹Department of Biology, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Plos Computational Biology

|August 13, 2013

Summary

This summary is machine-generated.

Evolutionary analysis reveals that structured RNAs, including riboswitches, often possess alternative conformations. These alternative structures are supported by sequence co-variation, suggesting they play functional roles in RNA regulation.

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Area of Science:

Molecular Biology
Bioinformatics
Evolutionary Biology

Background:

Structured RNAs exhibit sequence conservation and base-pair co-variation, indicating functional secondary structures.
Some RNAs, like riboswitches, require alternative secondary structures for gene regulation.
The evolutionary support for these alternative conformations is not fully understood.

Purpose of the Study:

To investigate the evolutionary co-variation supporting alternative RNA conformations.
To determine the extent of conservation of alternative secondary structures in various RNA classes.

Main Methods:

Extended sequence alignments to include terminator regions for purine riboswitches.
Applied Boltzmann suboptimal sampling to analyze RNA sequence ensembles.
Analyzed evolutionary co-variation in alignments of group I/II introns, tRNA, and other riboswitches.

Main Results:

Strong co-variation support was found for terminator, P1, and anti-terminator stems in purine riboswitches.
Purine riboswitch sequences appear evolved to favor specific alternative conformations.
Evidence for alternative conformations, compatible with the Boltzmann suboptimal ensemble, was found in a majority of analyzed RNAs.

Conclusions:

Alternative RNA conformations are evolutionarily selected for and likely play functional roles.
This selection pressure is present even in highly structured RNAs.
Findings support the functional importance of conformational flexibility in RNA.