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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 12, 2018 |
| Title |
Genome-wide CRISPR-Cas9 interrogation of splicing networks reveals a mechanism for recognition of autism-misregulated neuronal microexons [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Alternative splicing has critical roles in diverse cellular, developmental and pathological processes. However, the full repertoires of factors that control individual splicing events are not known. We describe a CRISPR-based screening strategy for the systematic identification of genes that control 3-27 nt microexons with functions in nervous system development and that are commonly disrupted in autism. Besides known regulators including nSR100/Srrm4, Rbfox and Ptbp1, approximately 200 additional genes impact microexon splicing. These genes are enriched in genetic links to autism. Two of the screen hits, Srsf11 and Rnps1, preferentially regulate Srrm4-dependent microexons relative to other exons. These factors form mutually stabilizing interactions with Srrm4 that bridge upstream intronic enhancer elements and exonic sequences to activate microexon splicing. Our study thus presents a system for the genome-wide definition of splicing regulatory networks and further reveals a mechanism for the recognition of microexons with critical roles in nervous system development and disorders.
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| Overall design |
RNA-Seq of N2A cells upon RNAi-mediated knockdown of Rnps1, Srrm3 and Srrm4, Srsf11, Rbfox2, or control non-targeting knockdown, in two replicates.
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| Contributor(s) |
Gonatopoulos-Pournatzis T, Wu M, Braunschweig U, Roth J, Han H, Best A, Raj B, Aregger M, O'Hanlon D, Ellis JD, Calarco JA, Moffat J, Gingras A, Blencowe BJ |
| Citation(s) |
30388412 |
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| Submission date |
Apr 02, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Ulrich Braunschweig |
| Organization name |
University of Toronto
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| Department |
Donnelly Centre
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| Lab |
Benjamin J. Blencowe
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| Street address |
160 College Street
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5S 3E1 |
| Country |
Canada |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| GSM3073878 |
RNA-Seq of N2A cells after non-targeting knockdown (control for Rnps1 knockdown), replicate 1 |
| GSM3073879 |
RNA-Seq of N2A cells after knockdown of Rnps1, replicate 1 |
| GSM3073880 |
RNA-Seq of N2A cells after non-targeting knockdown (control for Rnps1 knockdown), replicate 2 |
| GSM3073881 |
RNA-Seq of N2A cells after knockdown of Rnps1, replicate 2 |
| GSM3073882 |
RNA-Seq of N2A cells after non-targeting knockdown (control for Srrm3/Srrm4, Srsf11 and Rbfox2 knockdowns), replicate 1 |
| GSM3073883 |
RNA-Seq of N2A cells after knockdown of Srrm3 and Srrm4, replicate 1 |
| GSM3073884 |
RNA-Seq of N2A cells after knockdown of Srsf11, replicate 1 |
| GSM3073885 |
RNA-Seq of N2A cells after non-targeting knockdown (control for Srrm3/Srrm4, Srsf11 and Rbfox2 knockdowns), replicate 2 |
| GSM3073886 |
RNA-Seq of N2A cells after knockdown of Srrm3 and Srrm4, replicate 2 |
| GSM3073887 |
RNA-Seq of N2A cells after knockdown of Srsf11, replicate 2 |
| GSM3402084 |
RNA-Seq of N2A cells after knockdown of Rbfox2, replicate 1 |
| GSM3402085 |
RNA-Seq of N2A cells after knockdown of Rbfox2, replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE112601 |
Genome-wide CRISPR-Cas9 interrogation of splicing networks reveals a mechanism for recognition of autism-misregulated neuronal microexons |
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| Relations |
| BioProject |
PRJNA448433 |
| SRA |
SRP136943 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE112600_AltSplicing_Rnps1.tab.gz |
2.0 Mb |
(ftp)(http) |
TAB |
| GSE112600_AltSplicing_Srrm3.Srrm4_Srsf11_Rbfox2.tab.gz |
3.2 Mb |
(ftp)(http) |
TAB |
| GSE112600_Expression_Rnps1.tab.gz |
721.1 Kb |
(ftp)(http) |
TAB |
| GSE112600_Expression_Srrm3.Srrm4_Srsf11_Rbfox2.tab.gz |
1.5 Mb |
(ftp)(http) |
TAB |
| GSE112600_vast-tools.AltSplicing_Rnps1.tab.gz |
13.6 Mb |
(ftp)(http) |
TAB |
| GSE112600_vast-tools.AltSplicing_Srrm3.Srrm4_Srsf11_Rbfox2.tab.gz |
20.1 Mb |
(ftp)(http) |
TAB |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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