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PMID: 19401680 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Discovering structural cis-regulatory elements by modeling the behaviors of mRNAs.

Molecular systems biology ·Vol. 5 ·2009-00-00 ·Pages 268

Foat BC, Stormo GD

Abstract

Gene expression is regulated at each step from chromatin remodeling through translation and degradation. Several known RNA-binding regulatory proteins interact with specific RNA secondary structures in addition to specific nucleotides. To provide a more comprehensive understanding of the regulation of gene expression, we developed an integrative computational approach that leverages functional genomics data and nucleotide sequences to discover RNA secondary structure-defined cis-regulatory elements (SCREs). We applied our structural cis-regulatory element detector (StructRED) to microarray and mRNA sequence data from Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. We recovered the known specificities of Vts1p in yeast and Smaug in flies. In addition, we discovered six putative SCREs in flies and three in humans. We characterized the SCREs based on their condition-specific regulatory influences, the annotation of the transcripts that contain them, and their locations within transcripts. Overall, we show that modeling functional genomics data in terms of combined RNA structure and sequence motifs is an effective method for discovering the specificities and regulatory roles of RNA-binding proteins.

MeSH Terms
Algorithms Animals Base Sequence DNA, Intergenic/genetics Drosophila Proteins/metabolism Drosophila melanogaster/genetics Gene Expression Regulation, Fungal Humans Models, Genetic Molecular Sequence Data Nucleic Acid Conformation Open Reading Frames/genetics RNA Stability RNA, Messenger/chemistry,genetics RNA-Binding Proteins/metabolism Regulatory Sequences, Ribonucleic Acid/genetics Repressor Proteins/metabolism Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/metabolism
Chemicals
DNA, Intergenic Drosophila Proteins RNA, Messenger RNA-Binding Proteins Regulatory Sequences, Ribonucleic Acid Repressor Proteins Saccharomyces cerevisiae Proteins Vts1 protein, S cerevisiae smg protein, Drosophila
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Foat Barrett C
Department of Genetics, Center for Genome Sciences, Washington University School of Medicine, St Louis, MO 63108, USA.
Stormo Gary D
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Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
DOI
10.1038/msb.2009.24
Published
2009-00-00
Epub
2009-00-28
Pages
268
Language
English
Region
England
NLM ID
101235389
PMCID
PMC2683727
Subset
IM
Grants
NHGRI NIH HHS · R01 HG000249 · United States
NHGRI NIH HHS · HG00249 · United States
External Links
PubMed source DOI: 10.1038/msb.2009.24 PMC Full Text View journal details
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