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 re...

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Main Authors: Barrett C Foat, Gary D Stormo
Format: Article
Language:English
Published: Springer Nature 2009-04-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2009.24
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author Barrett C Foat
Gary D Stormo
author_facet Barrett C Foat
Gary D Stormo
author_sort Barrett C Foat
collection DOAJ
description 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.
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spelling doaj-art-cf3d5abcf5c5435f8bf3a372a83d679a2025-08-24T11:59:45ZengSpringer NatureMolecular Systems Biology1744-42922009-04-015111410.1038/msb.2009.24Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAsBarrett C Foat0Gary D Stormo1Department of Genetics, Center for Genome Sciences, Washington University School of MedicineDepartment of Genetics, Center for Genome Sciences, Washington University School of MedicineAbstract 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.https://doi.org/10.1038/msb.2009.24modelingmRNA stabilitypolysome associationpost‐transcriptional regulationsecondary structure
spellingShingle Barrett C Foat
Gary D Stormo
Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAs
Molecular Systems Biology
modeling
mRNA stability
polysome association
post‐transcriptional regulation
secondary structure
title Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAs
title_full Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAs
title_fullStr Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAs
title_full_unstemmed Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAs
title_short Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAs
title_sort discovering structural cis regulatory elements by modeling the behaviors of mrnas
topic modeling
mRNA stability
polysome association
post‐transcriptional regulation
secondary structure
url https://doi.org/10.1038/msb.2009.24
work_keys_str_mv AT barrettcfoat discoveringstructuralcisregulatoryelementsbymodelingthebehaviorsofmrnas
AT garydstormo discoveringstructuralcisregulatoryelementsbymodelingthebehaviorsofmrnas