Widespread purifying selection on RNA structure in mammals

Smith, Martin A., Gesell, Tanja, Stadler, Peter F. and Mattick, John S. (2013) Widespread purifying selection on RNA structure in mammals. Nucleic Acids Research, 41 17: 8220-8236. doi:10.1093/nar/gkt596

Author Smith, Martin A.
Gesell, Tanja
Stadler, Peter F.
Mattick, John S.
Title Widespread purifying selection on RNA structure in mammals
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
Publication date 2013-09-17
Year available 2013
Sub-type Article (original research)
DOI 10.1093/nar/gkt596
Open Access Status DOI
Volume 41
Issue 17
Start page 8220
End page 8236
Total pages 17
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Evolutionarily conserved RNA secondary structures are a robust indicator of purifying selection and, consequently, molecular function. Evaluating their genome-wide occurrence through comparative genomics has consistently been plagued by high false-positive rates and divergent predictions. We present a novel benchmarking pipeline aimed at calibrating the precision of genome-wide scans for consensus RNA structure prediction. The benchmarking data obtained from two refined structure prediction algorithms, RNAz and SISSIz, were then analyzed to fine-tune the parameters of an optimized workflow for genomic sliding window screens. When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies >4 million evolutionarily constrained RNA structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5–22%). These predictions comprise 13.6% of the human genome, 88% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional. As an example, our findings identify both known and novel conserved RNA structure motifs in the long noncoding RNA MALAT1. This study provides an extensive set of functional transcriptomic annotations that will assist researchers in uncovering the precise mechanisms underlying the developmental ontologies of higher eukaryotes.
Keyword Long noncoding RNAs
Secondary structure prediction
Consensus structure prediction
Multiple sequence alignments
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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