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| Status |
Public on Jan 15, 2015 |
| Title |
Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| 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.
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| Contributor(s) |
Madan V, Kanojia D, Li J, Okamoto R, Sato-Otsubo A, Kohlmann A, Sanada M, Grossmann V, Sundaresan J, Shiraishi Y, Miyano S, Thol F, Ganser A, Yang H, Haferlach T, Ogawa S, Koeffler HP |
| Citation(s) |
25586593 |
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| Submission date |
Dec 03, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Henry Yang |
| E-mail(s) |
csiyangh@nus.edu.sg
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| Organization name |
Cancer Science Institute of Singapore
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| Street address |
28 Medical Drive
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| City |
Singapore |
| ZIP/Postal code |
117456 |
| Country |
Singapore |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA269142 |
| SRA |
SRP050493 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63816_RAW.tar |
4.9 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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