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Series GSE57278 Query DataSets for GSE57278
Status Public on Sep 11, 2014
Title A global regulatory mechanism for activating an exon network required for neurogenesis
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The vertebrate and neural-specific SR-related protein nSR100/SRRM4 regulates an extensive program of alternative splicing with critical roles in nervous system development. However, the mechanism by which nSR100 controls its target exons is poorly understood. We demonstrate that nSR100-dependent neural exons are associated with a unique configuration of intronic cis-elements that promote rapid switch-like regulation during neurogenesis. A key feature of this configuration is the insertion of specialized intronic enhancers between polypyrimidine tracts and acceptor sites that bind nSR100 to potently activate exon inclusion in neural cells, while weakening 3' splice site recognition and contributing to exon skipping in non-neural cells. nSR100 further operates by forming multiple interactions with early spliceosome components bound proximal to 3' splice sites. These multifaceted interactions achieve dominance over neural exon silencing mediated by the splicing regulator PTBP1. The results thus illuminate a widespread mechanism by which a critical neural exon network is activated during neurogenesis.
Overall design RNA-Seq was used to obtain mRNA profiles of various N2A and 293T cell lines from human and mouse, respectively, to investigate the roles of nSR100, Ptbp1 and U2af65 in alternative splicing regulation. PAR-iCLIP and iCLIP experiments followed by high throughput sequencing were conducted to obtain RNA binding profiles of nSR100, PTBP1 and U2af65.
Contributor(s) Raj B, Irimia M, Braunschweig U, Sterne-Weiler T, O'Hanlon D, Lin Z, Chen GI, Easton L, Ule J, Gingras A, Eyras E, Blencowe B
Citation(s) 25219497
Submission date May 05, 2014
Last update date May 15, 2019
Contact name Bushra Raj
Organization name Harvard University
Street address 16 Divinity Avenue
City Cambridge
State/province MA
ZIP/Postal code 02138
Country USA
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (22)
GSM1378364 N2A_Ctrl_KDshGFP-1
GSM1378365 N2A_nSR100_KDshL4-1
GSM1378366 N2A_Ctrl_KDshGFP-2
BioProject PRJNA246157
SRA SRP041656

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE57278_293TnSR100_PariCLIP_pool2.bedgraph.gz 88.6 Mb (ftp)(http) BEDGRAPH
GSE57278_MmumRNA-50-CL_N2A_nSR100_Cont_exprRPKM.txt.gz 143.0 Kb (ftp)(http) TXT
GSE57278_MmumRNA-50-CL_N2A_nSR100_KD_exprRPKM.txt.gz 144.1 Kb (ftp)(http) TXT
GSE57278_RAW.tar 506.2 Mb (http)(custom) TAR (of BEDGRAPH, TXT)
SRA Run SelectorHelp
Processed data provided as supplementary file
Raw data are available in SRA

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