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GSE63816

GSE GEO
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Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome

Organism: Homo sapiens
Platform: GPL11154
Samples: 22
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Dec 03 2014
Last Updated: May 15 2019
Status: Public on Jan 15 2015
Contact: Henry,,Yang (Cancer Science Institute of Singapore)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA269142 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP050493

Summary

Somatic mutations in the spliceosome gene ZRSR2— located on the X chromosome — are associated with myelodysplastic syndrome (MDS). ZRSR2 is involved in the recognition of 3΄ splice site during the early stages of spliceosome assembly; however, its precise role in RNA splicing has remained unclear. Here, we characterize ZRSR2 as an essential component of the minor spliceosome (U12-dependent) assembly. shRNA mediated knockdown of ZRSR2 leads to impaired splicing of the U12-type introns, and RNA-Sequencing of MDS bone marrow reveals that loss of ZRSR2 activity causes increased mis-splicing. These splicing defects involve retention of the U12-type introns while splicing of the U2-type introns remain mostly unaffected. ZRSR2 deficient cells also exhibit reduced proliferation potential and distinct alterations in myeloid and erythroid differentiation in vitro. These data identify a specific role for ZRSR2 in RNA splicing and highlight dysregulated splicing of U12-type introns as a characteristic feature of ZRSR2 mutations in MDS.

Overall Design

RNA sequencing was performed on 16 bone marrow samples (MDS and normal) and six samples of control or ZRSR2 shRNA transduced TF-1 cells and data was analysed for aberrant splicing caused by ZRSR2 mutations/deficiency.

Analysis (6 steps)

View Data Processing
Processing steps for GSE63816
  1. Mapped the sequenced reads to the reference transcript in the database obtained from Refseq, Ensemble and UCSC known genes using bowtie.
  2. Unmapped or poorly mapped reads were realigned to human reference genome (hg19) with the Blat software.
  3. The mapped reads were organized into five different libraries 1) exon read library, 2) intron read library, 3) exon-intron junction read library, 4) exon-exon junction read library, and 5) intergenic read library.
  4. The gene classification was done using all known Refseq transcripts.
  5. Differential splicing analysis.
  6. Classification of introns.

Supplementary Files (1)

GSE63816_RAW.tar Download
GEO Samples (22)
GSM1558056 GSM1558057 GSM1558058 GSM1558059 GSM1558060 GSM1558061 GSM1558062 GSM1558063 GSM1558064 GSM1558065 GSM1558066 GSM1558067 GSM1558068 GSM1558069 GSM1558070 GSM1558071 GSM1558072 GSM1558073 GSM1558074 GSM1558075 GSM1558076 GSM1558077

Dataset Citations (1)

PubMed citation (PMID 25586593)

SRA Experiments (22) and Runs (22)

Total: 198173 MB
SRX794516 SRP050493 RNA-Seq PAIRED
GSM1558056: ZRSR2 mutant MDS 1; Homo sapiens; RNA-Seq
Sample: SRS778025
BioProject: PRJNA269142
BioSample: SAMN03251983
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 59
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691633 68549315 13709863000 8456.72 ZRSR2_mut_MDS_1_R1.fastq.bz2, SRR1691633.sralite, SRR1691633, ZRSR2_m… SRA
SRX794517 SRP050493 RNA-Seq PAIRED
GSM1558057: ZRSR2 mutant MDS 2; Homo sapiens; RNA-Seq
Sample: SRS778023
BioProject: PRJNA269142
BioSample: SAMN03251979
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 81
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691634 65777635 13155527000 8081.39 SRR1691634, SRR1691634.sralite, ZRSR2_mut_MDS_2_R2.fastq.bz2, ZRSR2_m… SRA
SRX794518 SRP050493 RNA-Seq PAIRED
GSM1558058: ZRSR2 mutant MDS 3; Homo sapiens; RNA-Seq
Sample: SRS778024
BioProject: PRJNA269142
BioSample: SAMN03251982
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 70
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691635 68822459 13764491800 8450.29 ZRSR2_mut_MDS_3_R1.fastq.bz2, SRR1691635, SRR1691635.sralite, ZRSR2_m… SRA
SRX794519 SRP050493 RNA-Seq PAIRED
GSM1558059: ZRSR2 mutant MDS 4; Homo sapiens; RNA-Seq
Sample: SRS778027
BioProject: PRJNA269142
BioSample: SAMN03251980
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 74
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691636 79263018 15852603600 9783.31 ZRSR2_mut_MDS_4_R1.fastq.bz2, SRR1691636, SRR1691636.sralite, ZRSR2_m… SRA
SRX794520 SRP050493 RNA-Seq PAIRED
GSM1558060: ZRSR2 mutant MDS 5; Homo sapiens; RNA-Seq
Sample: SRS778028
BioProject: PRJNA269142
BioSample: SAMN03251981
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 72
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691637 65780601 13156120200 8055.74 SRR1691637, SRR1691637.sralite, ZRSR2_mut_MDS_5_R2.fastq.bz2, ZRSR2_m… SRA
SRX794521 SRP050493 RNA-Seq PAIRED
GSM1558061: ZRSR2 mutant MDS 6; Homo sapiens; RNA-Seq
Sample: SRS778026
BioProject: PRJNA269142
BioSample: SAMN03251997
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 74
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691638 65918921 13183784200 8055.0 ZRSR2_mut_MDS_6_R1.fastq.bz2, SRR1691638.sralite, SRR1691638, ZRSR2_m… SRA
SRX794522 SRP050493 RNA-Seq PAIRED
GSM1558062: ZRSR2 mutant MDS 7; Homo sapiens; RNA-Seq
Sample: SRS778029
BioProject: PRJNA269142
BioSample: SAMN03251991
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 62
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691639 81928806 16385761200 10575.67 ZRSR2_mut_MDS_7_R2.fastq.bz2, SRR1691639, SRR1691639.sralite, ZRSR2_m… SRA
SRX794523 SRP050493 RNA-Seq PAIRED
GSM1558063: ZRSR2 mutant MDS 8; Homo sapiens; RNA-Seq
Sample: SRS778031
BioProject: PRJNA269142
BioSample: SAMN03251995
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 72
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691640 66723482 13344696400 8552.41 ZRSR2_mut_MDS_8_R1.fastq.bz2, SRR1691640, SRR1691640.sralite, ZRSR2_m… SRA
SRX794524 SRP050493 RNA-Seq PAIRED
GSM1558064: ZRSR2 wild type MDS 1; Homo sapiens; RNA-Seq
Sample: SRS778030
BioProject: PRJNA269142
BioSample: SAMN03251990
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 50
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691641 92086842 18233194716 11490.23 ZRSR2_WT_MDS_1_R1.fastq.bz2, ZRSR2_WT_MDS_1_R2.fastq.bz2, SRR1691641,… SRA
SRX794525 SRP050493 RNA-Seq PAIRED
GSM1558065: ZRSR2 wild type MDS 2; Homo sapiens; RNA-Seq
Sample: SRS778032
BioProject: PRJNA269142
BioSample: SAMN03251986
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 76
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691642 76214625 15090495750 9567.64 ZRSR2_WT_MDS_2_R1.fastq.bz2, ZRSR2_WT_MDS_2_R2.fastq.bz2, SRR1691642,… SRA
SRX794526 SRP050493 RNA-Seq PAIRED
GSM1558066: ZRSR2 wild type MDS 3; Homo sapiens; RNA-Seq
Sample: SRS778034
BioProject: PRJNA269142
BioSample: SAMN03251998
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 65
gender: female
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691643 61668892 12210440616 7693.81 SRR1691643, SRR1691643.sralite, ZRSR2_WT_MDS_3_R2.fastq.bz2, ZRSR2_WT… SRA
SRX794527 SRP050493 RNA-Seq PAIRED
GSM1558067: ZRSR2 wild type MDS 4; Homo sapiens; RNA-Seq
Sample: SRS778033
BioProject: PRJNA269142
BioSample: SAMN03251984
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: myelodysplastic syndrome (MDS)
age: 71
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691644 82172308 16434461600 10516.77 SRR1691644.sralite, SRR1691644, ZRSR2_WT_MDS_4_R2.fastq.bz2, ZRSR2_WT… SRA
SRX794528 SRP050493 RNA-Seq PAIRED
GSM1558068: Normal bone marrow 1; Homo sapiens; RNA-Seq
Sample: SRS778035
BioProject: PRJNA269142
BioSample: SAMN03251989
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: normal
age: 62
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691645 68253150 13650630000 8783.52 SRR1691645.sralite, SRR1691645, Normal_BM_1_R2.fastq.bz2, Normal_BM_1… SRA
SRX794529 SRP050493 RNA-Seq PAIRED
GSM1558069: Normal bone marrow 2; Homo sapiens; RNA-Seq
Sample: SRS778036
BioProject: PRJNA269142
BioSample: SAMN03251985
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: normal
age: 51
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691646 64709278 12941855600 8273.35 SRR1691646, SRR1691646.sralite, Normal_BM_2_R2.fastq.bz2, Normal_BM_2… SRA
SRX794530 SRP050493 RNA-Seq PAIRED
GSM1558070: Normal bone marrow 3; Homo sapiens; RNA-Seq
Sample: SRS778037
BioProject: PRJNA269142
BioSample: SAMN03252000
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: normal
age: 38
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691647 68883377 13638908646 8258.76 SRR1691647, SRR1691647.sralite, Normal_BM_3_R2.fastq.bz2, Normal_BM_3… SRA
SRX794531 SRP050493 RNA-Seq PAIRED
GSM1558071: Normal bone marrow 4; Homo sapiens; RNA-Seq
Sample: SRS778039
BioProject: PRJNA269142
BioSample: SAMN03251999
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: bone marrow
disease: normal
age: 75
gender: male
Original files (1)
bone marrow
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691648 69400439 13741286922 8378.85 Normal_BM_4_R1.fastq.bz2, Normal_BM_4_R2.fastq.bz2, SRR1691648, SRR16… SRA
SRX794532 SRP050493 RNA-Seq PAIRED
GSM1558072: TF-1 control shRNA experiment 1; Homo sapiens; RNA-Seq
Sample: SRS778038
BioProject: PRJNA269142
BioSample: SAMN03251994
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TF-1 cell line
disease: erythroleukemia
age: 35
gender: male
Original files (1)
TF-1 cell line
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691649 66222691 13244538200 8493.08 TF1_con_sh_1_R1.fastq.bz2, TF1_con_sh_1_R2.fastq.bz2, SRR1691649, SRR… SRA
SRX794533 SRP050493 RNA-Seq PAIRED
GSM1558073: TF-1 ZRSR2 shRNA1 experiment 1; Homo sapiens; RNA-Seq
Sample: SRS778040
BioProject: PRJNA269142
BioSample: SAMN03251987
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TF-1 cell line
disease: erythroleukemia
age: 35
gender: male
Original files (1)
TF-1 cell line
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691650 76538024 15307604800 9889.31 TF1_ZRSR2_sh1_1_R1.fastq.bz2, TF1_ZRSR2_sh1_1_R2.fastq.bz2, SRR169165… SRA
SRX794534 SRP050493 RNA-Seq PAIRED
GSM1558074: TF-1 ZRSR2 shRNA2 experiment 1; Homo sapiens; RNA-Seq
Sample: SRS778041
BioProject: PRJNA269142
BioSample: SAMN03251993
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TF-1 cell line
disease: erythroleukemia
age: 35
gender: male
Original files (1)
TF-1 cell line
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691651 70338581 14067716200 9084.41 TF1_ZRSR2_sh2_1_R1.fastq.bz2, SRR1691651, SRR1691651.sralite, TF1_ZRS… SRA
SRX794535 SRP050493 RNA-Seq PAIRED
GSM1558075: TF-1 control shRNA experiment 2; Homo sapiens; RNA-Seq
Sample: SRS778042
BioProject: PRJNA269142
BioSample: SAMN03251988
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TF-1 cell line
disease: erythroleukemia
age: 35
gender: male
Original files (1)
TF-1 cell line
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691652 78813199 15762639800 10150.65 TF1_con_sh_2_R1.fastq.bz2, TF1_con_sh_2_R2.fastq.bz2, SRR1691652, SRR… SRA
SRX794536 SRP050493 RNA-Seq PAIRED
GSM1558076: TF-1 ZRSR2 shRNA1 experiment 2; Homo sapiens; RNA-Seq
Sample: SRS778043
BioProject: PRJNA269142
BioSample: SAMN03251996
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TF-1 cell line
disease: erythroleukemia
age: 35
gender: male
Original files (1)
TF-1 cell line
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691653 70905934 14181186800 9065.86 TF1_ZRSR2_sh1_2_R1.fastq.bz2, TF1_ZRSR2_sh1_2_R2.fastq.bz2, SRR169165… SRA
SRX794537 SRP050493 RNA-Seq PAIRED
GSM1558077: TF-1 ZRSR2 shRNA2 experiment 2; Homo sapiens; RNA-Seq
Sample: SRS778046
BioProject: PRJNA269142
BioSample: SAMN03251992
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TF-1 cell line
disease: erythroleukemia
age: 35
gender: male
Original files (1)
TF-1 cell line
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR1691654 66581424 13316284800 8516.26 TF1_ZRSR2_sh2_2_R1.fastq.bz2, TF1_ZRSR2_sh2_2_R2.fastq.bz2, SRR169165… SRA

Linked Publications (1)

Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms.
Cancer discovery · 2022

Data Files (22)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— Normal_BM_4_R1.fastq.bz2 RNA-Seq 8.2 GB link
— SRR1691634 RNA-Seq 7.9 GB link
— SRR1691637 RNA-Seq 7.9 GB link
— SRR1691643 RNA-Seq 7.5 GB link
— SRR1691644.sralite RNA-Seq 10.3 GB link
— SRR1691645.sralite RNA-Seq 8.6 GB link
— SRR1691646 RNA-Seq 8.1 GB link
— SRR1691647 RNA-Seq 8.1 GB link
— TF1_con_sh_1_R1.fastq.bz2 RNA-Seq 8.3 GB link
— TF1_con_sh_2_R1.fastq.bz2 RNA-Seq 9.9 GB link
— TF1_ZRSR2_sh1_1_R1.fastq.bz2 RNA-Seq 9.7 GB link
— TF1_ZRSR2_sh1_2_R1.fastq.bz2 RNA-Seq 8.9 GB link
— TF1_ZRSR2_sh2_1_R1.fastq.bz2 RNA-Seq 8.9 GB link
— TF1_ZRSR2_sh2_2_R1.fastq.bz2 RNA-Seq 8.3 GB link
— ZRSR2_mut_MDS_1_R1.fastq.bz2 RNA-Seq 8.3 GB link
— ZRSR2_mut_MDS_3_R1.fastq.bz2 RNA-Seq 8.3 GB link
— ZRSR2_mut_MDS_4_R1.fastq.bz2 RNA-Seq 9.6 GB link
— ZRSR2_mut_MDS_6_R1.fastq.bz2 RNA-Seq 7.9 GB link
— ZRSR2_mut_MDS_7_R2.fastq.bz2 RNA-Seq 10.3 GB link
— ZRSR2_mut_MDS_8_R1.fastq.bz2 RNA-Seq 8.4 GB link
— ZRSR2_WT_MDS_1_R1.fastq.bz2 RNA-Seq 11.2 GB link
— ZRSR2_WT_MDS_2_R1.fastq.bz2 RNA-Seq 9.3 GB link