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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 [SPAR-seq] |
| Organism |
Mus musculus |
| Experiment type |
Other
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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 |
Alternative splicing of selected endogenous genes was monitored in 24 siRNA-mediated knockdowns, including controls, in N2A mouse neuroblastoma cells in duplicate.
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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 |
Sep 19, 2018 |
| Last update date |
Jan 27, 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) |
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| Samples (48)
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| GSM3395134 |
SPAR-Seq of multi-exon regions of selected genes in N2A, untreated (T001), replicate 1 |
| GSM3395135 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srrm4 knockdown (T002), replicate 1 |
| GSM3395136 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srrm3 knockdown (T003), replicate 1 |
| GSM3395137 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Rbfox2 knockdown (T004), replicate 1 |
| GSM3395138 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Elavl2 knockdown (T005), replicate 1 |
| GSM3395139 |
SPAR-Seq of multi-exon regions of selected genes in N2A, hnRNP K knockdown (T006), replicate 1 |
| GSM3395140 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Gpatch8 knockdown (T007), replicate 1 |
| GSM3395141 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Rnps1 knockdown (T008), replicate 1 |
| GSM3395142 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Cdc5l knockdown (T009), replicate 1 |
| GSM3395143 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Strbp knockdown (T010), replicate 1 |
| GSM3395144 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Fxr1 knockdown (T011), replicate 1 |
| GSM3395145 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ep300 knockdown (T012), replicate 1 |
| GSM3395146 |
SPAR-Seq of multi-exon regions of selected genes in N2A, CBP knockdown (T013), replicate 1 |
| GSM3395147 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Hira knockdown (T014), replicate 1 |
| GSM3395148 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Fam133b knockdown (T015), replicate 1 |
| GSM3395149 |
SPAR-Seq of multi-exon regions of selected genes in N2A, control non-targeting knockdown (T016), replicate 1 |
| GSM3395150 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ptbp1 knockdown (T017), replicate 1 |
| GSM3395151 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Qk knockdown (T018), replicate 1 |
| GSM3395152 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Fbxw11 knockdown (T019), replicate 1 |
| GSM3395153 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ippk knockdown (T020), replicate 1 |
| GSM3395154 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ncbp1 knockdown (T021), replicate 1 |
| GSM3395155 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Rbm17 knockdown (T022), replicate 1 |
| GSM3395156 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srsf6 knockdown (T023), replicate 1 |
| GSM3395157 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srrm4+siSrrm3 knockdown (T024), replicate 1 |
| GSM3395158 |
SPAR-Seq of multi-exon regions of selected genes in N2A, untreated (T001), replicate 2 |
| GSM3395159 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srrm4 knockdown (T002), replicate 2 |
| GSM3395160 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srrm3 knockdown (T003), replicate 2 |
| GSM3395161 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Rbfox2 knockdown (T004), replicate 2 |
| GSM3395162 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Elavl2 knockdown (T005), replicate 2 |
| GSM3395163 |
SPAR-Seq of multi-exon regions of selected genes in N2A, hnRNP K knockdown (T006), replicate 2 |
| GSM3395164 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Gpatch8 knockdown (T007), replicate 2 |
| GSM3395165 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Rnps1 knockdown (T008), replicate 2 |
| GSM3395166 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Cdc5l knockdown (T009), replicate 2 |
| GSM3395167 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Strbp knockdown (T010), replicate 2 |
| GSM3395168 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Fxr1 knockdown (T011), replicate 2 |
| GSM3395169 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ep300 knockdown (T012), replicate 2 |
| GSM3395170 |
SPAR-Seq of multi-exon regions of selected genes in N2A, CBP knockdown (T013), replicate 2 |
| GSM3395171 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Hira knockdown (T014), replicate 2 |
| GSM3395172 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Fam133b knockdown (T015), replicate 2 |
| GSM3395173 |
SPAR-Seq of multi-exon regions of selected genes in N2A, control non-targeting knockdown (T016), replicate 2 |
| GSM3395174 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ptbp1 knockdown (T017), replicate 2 |
| GSM3395175 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Qk knockdown (T018), replicate 2 |
| GSM3395176 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Fbxw11 knockdown (T019), replicate 2 |
| GSM3395177 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ippk knockdown (T020), replicate 2 |
| GSM3395178 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Ncbp1 knockdown (T021), replicate 2 |
| GSM3395179 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Rbm17 knockdown (T022), replicate 2 |
| GSM3395180 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srsf6 knockdown (T023), replicate 2 |
| GSM3395181 |
SPAR-Seq of multi-exon regions of selected genes in N2A, Srrm4+siSrrm3 knockdown (T024), 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 |
PRJNA491823 |
| SRA |
SRP162100 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120164_InclExclCounts.tab.gz |
30.5 Kb |
(ftp)(http) |
TAB |
| GSE120164_Junctions108_11-101_fwd.fa.gz |
7.2 Kb |
(ftp)(http) |
FA |
| GSE120164_Junctions108_11-101_rev.fa.gz |
7.5 Kb |
(ftp)(http) |
FA |
| GSE120164_KnockdownAnnotation.tab.gz |
1.1 Kb |
(ftp)(http) |
TAB |
| GSE120164_PSI.SSMD.tab.gz |
6.0 Kb |
(ftp)(http) |
TAB |
| GSE120164_ScreenEvents_junctions.tab.gz |
1.2 Kb |
(ftp)(http) |
TAB |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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