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Open Access Research article

Quantifying the relationship between sequence and three-dimensional structure conservation in RNA

Emidio Capriotti12 and Marc A Marti-Renom1*

Author Affiliations

1 Structural Genomics Unit, Bioinformatics and Genomics Department, Centro de Investigación Príncipe Felipe, Valencia, Spain

2 Current Address: The Helix Group, Department of Bioengineering, Stanford University, Stanford, CA 94305-5444, USA

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BMC Bioinformatics 2010, 11:322  doi:10.1186/1471-2105-11-322

Published: 15 June 2010

Abstract

Background

In recent years, the number of available RNA structures has rapidly grown reflecting the increased interest on RNA biology. Similarly to the studies carried out two decades ago for proteins, which gave the fundamental grounds for developing comparative protein structure prediction methods, we are now able to quantify the relationship between sequence and structure conservation in RNA.

Results

Here we introduce an all-against-all sequence- and three-dimensional (3D) structure-based comparison of a representative set of RNA structures, which have allowed us to quantitatively confirm that: (i) there is a measurable relationship between sequence and structure conservation that weakens for alignments resulting in below 60% sequence identity, (ii) evolution tends to conserve more RNA structure than sequence, and (iii) there is a twilight zone for RNA homology detection.

Discussion

The computational analysis here presented quantitatively describes the relationship between sequence and structure for RNA molecules and defines a twilight zone region for detecting RNA homology. Our work could represent the theoretical basis and limitations for future developments in comparative RNA 3D structure prediction.