Genome-wide determination of a broad ESRP-regulated posttranscriptional network by high-throughput sequencing

Kimberly A. Dittmar, Peng Jiang, Juw Won Park, Karine Amirikian, Ji Wan, Shihao Shen, Yi Xing, Russell P. Carstens

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

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.

Original languageEnglish
Pages (from-to)1468-1482
Number of pages15
JournalMolecular and cellular biology
Volume32
Issue number8
DOIs
StatePublished - Apr 2012

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