title: Genome-wide determination of a broad ESRP-regulated posttranscriptional network by high-throughput sequencing.
abstract: Tissue-specific alternative splicing is achieved through the coordinated assembly of RNA binding proteins at specific sites to enhance or silence splicing at nearby splice sites. We used high-throughput sequencing (RNA-Seq) to investigate the complete spectrum of alternative splicing events that are regulated by the epithelium-specific splicing regulatory proteins ESRP1 and ESRP2. We also combined this analysis with direct RNA sequencing (DRS) to reveal ESRP-mediated regulation of alternative polyadenylation. To define binding motifs that mediate direct regulation of splicing and polyadenylation by ESRP, SELEX-Seq analysis was performed, coupling traditional SELEX with high-throughput sequencing. Identification and scoring of high-affinity ESRP1 binding motifs within ESRP target genes allowed the generation of RNA maps that define the position-dependent activity of the ESRPs in regulating cassette exons and alternative 3' ends. These extensive analyses provide a comprehensive picture of the functions of the ESRPs in an epithelial posttranscriptional gene expression program.
authors.affiliation: Renal Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Dittmar
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Juw Won
authors.initials: JW
authors.lastname: Park
authors.forename: Karine
authors.initials: K
authors.lastname: Amirikian
authors.forename: Ji
authors.initials: J
authors.lastname: Wan
authors.forename: Shihao
authors.initials: S
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
authors.forename: Russell P
authors.initials: RP
authors.lastname: Carstens
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D001665:Binding Sites; D004848:Epithelium / Q000378:metabolism*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D059372:Nucleotide Motifs; D009928:Organ Specificity; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: C539364:ESRP1 protein, human; C539365:ESRP2 protein, human; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins