期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 32, 期 8, 页码 1468-1482出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.06536-11
关键词
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资金
- NIH [UL1 RR024979, R01 GM088809, R01 GM088342, P30 DK054759, T32HL007638]
- Edward Mallinckrodt Jr. Foundation
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.
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