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Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo.

Abstract：

:Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ∼ 11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in patients with MDS.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Shirai CL,Ley JN,White BS,Kim S,Tibbitts J,Shao J,Ndonwi M,Wadugu B,Duncavage EJ,Okeyo-Owuor T,Liu T,Griffith M,McGrath S,Magrini V,Fulton RS,Fronick C,O'Laughlin M,Graubert TA,Walter MJ

doi

10.1016/j.ccell.2015.04.008

subject

Has Abstract

pub_date

2015-05-11 00:00:00

pages

631-43

issue

5

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(15)00141-5

journal_volume

27

pub_type

杂志文章

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