10.5061/DRYAD.K648S
Jin, Shuiling
Zhengzhou University
University of Alabama at Birmingham
Su, Hairui
University of Alabama at Birmingham
Tran, Ngoc-Tung
University of Alabama at Birmingham
Song, Jing
Zhengzhou University
Lu, Sydney S.
Memorial Sloan Kettering Cancer Center
Li, Ying
Macau University of Science and Technology
Huang, Suming
University of Florida
Abdel-Wahab, Omar
Memorial Sloan Kettering Cancer Center
Liu, Yanyan
Zhengzhou University
Zhao, Xinyang
University of Alabama at Birmingham
Data from: Splicing factor SF3B1K700E mutant dysregulates erythroid
differentiation via aberrant alternative splicing of transcription factor
TAL1
Dryad
dataset
2018
RBM15
PRMT1
TAL1
Homo Sapiens
SF3b1
2018-04-03T00:00:00Z
2018-04-03T00:00:00Z
en
https://doi.org/10.1371/journal.pone.0175523
43381 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
More than 60% of myeloid dysplasia syndrome (MDS) contains mutations in
genes encoding for splicing factors such as SF3B1, U2AF, SRSF2 and ZRSR2.
Mutations in SF3B1 are associated with 80% cases of refractory anemia with
ring sideroblast (RARS), a subtype of MDS. SF3B1K700E is the most
frequently mutated site among mutations on SF3B1. Yet the molecular
mechanisms on how mutations of splicing factors lead to defective
erythropoiesis are not clear. SF3B1K700E mutant binds to an RNA binding
protein, RBM15, stronger than the wild type SF3B1 protein in
co-immunoprecipitation assays. In addition, K700E mutant alters the RNA
splicing of transcription factors TAL1 and GATA1. Via alternative RNA
splicing, a novel short TAL1 transcript variant (TAL1s) is generated.
Enhanced interaction between SF3B1 and RBM15 promotes the production of
full-length TAL1 (TAL1fl) mRNA, while reduction of RBM15 protein level via
PRMT1-mediated degradation pathway changes TAL1s/TAL1fl ratio in favor of
TAL1s. TAL1s contains the helix-loop-helix DNA binding domain but not the
N terminal region upstream of the DNA binding domain. The TAL1s protein
loses its interaction with ETO2, which represses early erythropoiesis. In
this vein, overexpression of TAL1s stimulates the transcription of
β-hemoglobin in human leukemia K562 cells and promotes erythroid
differentiation of human cord blood CD34+ cells cultured in
erythropoietin-containing medium. Therefore, mutations of SF3B1 may block
erythropoiesis via dysregulation of alternative RNA splicing of
transcription factor TAL1, and targeting PRMT1 may alleviate the anemic
symptoms in MDS patients.
raw data for charts in figuresThis file contains real time PCR data for
all the figures and western blot band quantification in figure 2.support
information.xlsx