Transcriptomics

Dataset Information

416

RNA-seq of bone marrow from patients with myelodysplastic syndrome


ABSTRACT: 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. 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: H P Koeffler   Jia Li  Masashi Sanada  Ryoko Okamoto  Vera Grossmann  Arnold Ganser  Satoru Miyano  Alexander Kohlmann  Janani Sundaresan  Seishi Ogawa  Torsten Haferlach  Yuichi Shiraishi  Vikas Madan  Felicitas Thol  Aiko Sato-Otsubo  Deepika Kanojia  Henry Yang 

PROVIDER: E-GEOD-63816 | ArrayExpress | 2015-01-15

SECONDARY ACCESSION(S): SRP050493GSE63816PRJNA269142

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications


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-sequenc  ...[more]

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