Wild-type Splicing Factor U2AF1 inhibits splicing associated with a recurrent U2AF1 mutant in human lung cancers and is required for cell survival
نویسندگان
چکیده
1. Cancer Biology Section, Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892, United States 2. Department of Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, United States 3. Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, United States 4. Genetics Branch, National Cancer Institute, Bethesda, Maryland, 20892, United States 5. Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States 6. Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United States
منابع مشابه
Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival
We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analy...
متن کاملWild - type U 2 AF 1 antagonizes the splicing program characteristic of U 2 AF 1 - 1 mutant tumors and is required for cell survival
31. CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not. doi: bioRxiv preprint first posted online Apr. 13, 2016;. CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not. doi: bioRxiv preprint first p...
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Recently, recurrent mutations of spliceosomal genes were frequently identified in myeloid malignancies, as well as other types of cancers. One of these spliceosomal genes, U2AF1, was affected by canonical somatic mutations in aggressive type of myeloid malignancies. We hypothesized that U2AF1 mutations causes defects of splicing (missplicing) in specific genes and that such misspliced genes mig...
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Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA). U...
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Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant ...
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