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Widespread purifying selection on RNA structure in mammals.

Martin A Smith¹, Tanja Gesell, Peter F Stadler

¹RNA Biology and Plasticity Laboratory, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 Australia, Genomics and Computational Biology Division, Institute for Molecular Bioscience, 306 Carmody Rd, University of Queensland, Brisbane, 4067 Australia, Department of Structural and Computational Biology; and Center for Integrative Bioinformatics Vienna (CIBIV), Max F. Perutz Laboratories (MFPL), University of Vienna, Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria, Bioinformatics Group, Department of Computer Science; and Interdisciplinary Center for Bioinformatics, University of Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany, Center for Non-coding RNA in Technology and Health, Department of Basic Veterinary and Animal Sciences, Faculty of Life Sciences University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C Denmark, Santa Fe Institute, 1399 Hyde Park Rd, Santa Fe, NM 87501, USA and St Vincent's Clinical School, University of New South Wales, Level 5, de Lacy, Victoria St, St Vincent's Hospital, Sydney, NSW 2010 Australia.

Nucleic Acids Research

|July 13, 2013

Summary

Researchers identified over 4 million conserved RNA structures in the mammalian genome, suggesting widespread functional elements beyond known genes. This discovery aids in understanding genome function and eukaryotic development.

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Area of Science:

Genomics
Molecular Biology
Bioinformatics

Background:

Evolutionarily conserved RNA secondary structures indicate molecular function and purifying selection.
Genome-wide identification of these structures is challenged by high false-positive rates and prediction variability.

Purpose of the Study:

To develop and validate a novel benchmarking pipeline for precise genome-wide RNA structure prediction.
To optimize parameters for genomic scans using RNAz and SISSIz algorithms.

Main Methods:

A novel benchmarking pipeline was created to calibrate precision in genome-wide RNA structure prediction.
Parameters for RNAz and SISSIz were refined using benchmarking data.
An optimized workflow was applied to multiple genome alignments of 35 mammals.

Main Results:

Over 4 million evolutionarily constrained RNA structures were identified in mammals with low false discovery rates (5-22%).
These structures constitute 13.6% of the human genome, with 88% located outside known constrained elements.
Conserved RNA structure motifs, including novel ones in MALAT1, were identified.

Conclusions:

The study reveals a substantial portion of the mammalian genome is functional, indicated by conserved RNA structures.
The findings provide extensive functional transcriptomic annotations for future research.
This work will aid in elucidating mechanisms of developmental ontologies in higher eukaryotes.