| Literature DB >> 30107174 |
Stanley Chun-Wei Lee1, Khrystyna North2, Eunhee Kim3, Eunjung Jang3, Esther Obeng4, Sydney X Lu1, Bo Liu1, Daichi Inoue1, Akihide Yoshimi1, Michelle Ki1, Mirae Yeo3, Xiao Jing Zhang1, Min Kyung Kim1, Hana Cho1, Young Rock Chung1, Justin Taylor1, Benjamin H Durham1, Young Joon Kim1, Alessandro Pastore1, Sebastien Monette5, James Palacino6, Michael Seiler6, Silvia Buonamici6, Peter G Smith6, Benjamin L Ebert4, Robert K Bradley7, Omar Abdel-Wahab8.
Abstract
Mutations affecting RNA splicing factors are the most common genetic alterations in myelodysplastic syndrome (MDS) patients and occur in a mutually exclusive manner. The basis for the mutual exclusivity of these mutations and how they contribute to MDS is not well understood. Here we report that although different spliceosome gene mutations impart distinct effects on splicing, they are negatively selected for when co-expressed due to aberrant splicing and downregulation of regulators of hematopoietic stem cell survival and quiescence. In addition to this synthetic lethal interaction, mutations in the splicing factors SF3B1 and SRSF2 share convergent effects on aberrant splicing of mRNAs that promote nuclear factor κB signaling. These data identify shared consequences of splicing-factor mutations and the basis for their mutual exclusivity.Entities:
Keywords: NF-κB; SF3B1; SRSF2; U2AF1; myelodysplastic syndromes; splicing
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Year: 2018 PMID： 30107174 PMCID： PMC6373472 DOI： 10.1016/j.ccell.2018.07.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743