title: Discovering structural cis-regulatory elements by modeling the behaviors of mRNAs.
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.
authors.affiliation: Department of Genetics, Center for Genome Sciences, Washington University School of Medicine, St Louis, MO 63108, USA.
authors.forename: Barrett C
authors.initials: BC
authors.lastname: Foat
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stormo
mesh_terms: D000465:Algorithms; D000818:Animals; D001483:Base Sequence; D021901:DNA, Intergenic / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D021901:DNA, Intergenic; D029721:Drosophila Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C508663:Vts1 protein, S cerevisiae; C402587:smg protein, Drosophila