U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SRX4714555: GSM3395155: SPAR-Seq of multi-exon regions of selected genes in N2A, Rbm17 knockdown (T022), replicate 1; Mus musculus; OTHER
1 ILLUMINA (Illumina MiSeq) run: 119,156 spots, 36M bases, 23.7Mb downloads

Submitted by: NCBI (GEO)
Study: Genome-wide CRISPR-Cas9 interrogation of splicing networks reveals a mechanism for recognition of autism-misregulated neuronal microexons [SPAR-seq]
show Abstracthide Abstract
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. Overall design: Alternative splicing of selected endogenous genes was monitored in 24 siRNA-mediated knockdowns, including controls, in N2A mouse neuroblastoma cells in duplicate.
Sample: SPAR-Seq of multi-exon regions of selected genes in N2A, Rbm17 knockdown (T022), replicate 1
SAMN10089653 • SRS3800265 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: Illumina MiSeq
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: PAIRED
Construction protocol: Forty-eight hours post-transfection, total RNA were purified from cultured cells using RNeasy Mini Kit (Qiagen), as per the manufacturer's instructions. For each sample, a multiplex RT-PCR assay was first applied to simultaneously amplify multi-exonic regions within 108 genes in a single reaction. The multiplex RT-PCR reaction was carried out in 96-well plates using the OneStep RT-PCR kit (Qiagen) as recommended by the manufacturer, with the following changes: reactions were performed in a volume of 20 uL with 2 uL of the purified total RNA as input, and a mixture of 50 pairs of primers was added to each reaction with a final concentration of 0.25 uM for each individual forward and reverse primer. Thermocycler settings were: 50°C for 30 minutes, 95°C for 15 minute, 30 cycles of 94°C for 40 seconds, 58°C for 1 minute (slow ramp rate), 72°C for 3 minutes, and a final extension step at 72°C for 10 minutes. Two sets of barcodes were incorporated into forward and reverse primers, respectively, after the universal adaptors and added to the amplicons in the second PCR reaction to allow demultiplexing all reads that were derived from a particular treatment. Primers sequences were: forward primer, AATGATACGGCGACCACCGAGATCTACACNNNNNNNNACACTCTTTCCCTACACGACGCTCTTCCGATCT (N denotes i5 barcode); reverse primer, CAAGCAGAAGACGGCATACGAGATNNNNNNNNGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT (N denotes i7 primer). The second PCR was performed using Phusion High-Fidelity DNA Polymerase (Thermo Scientific), as per the manufacturer's instructions. For each 20 uL of reaction, 1 uL of the multiplex RT-PCR reaction products was used as templates. The thermal cycling conditions were as follows: 98°C for 30 seconds, 15 cycles of 98°C for 10 seconds, 65°C for 30 seconds, 72°C for 30 seconds, and a final extension step at 72°C for 5 minutes. The resulting libraries were pooled and sequenced.
Experiment attributes:
GEO Accession: GSM3395155
Links:
Runs: 1 run, 119,156 spots, 36M bases, 23.7Mb
Run# of Spots# of BasesSizePublished
SRR7875696119,15636M23.7Mb2018-10-14

ID:
6380890

Supplemental Content

Search details

See more...

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...