The RNA-binding protein QKI suppresses cancer-associated aberrant splicing.
| Autor: | Feng-Yang Zong, Xing Fu, Wen-Juan Wei, Ya-Ge Luo, Monika Heiner, Li-Juan Cao, Zhaoyuan Fang, Rong Fang, Daru Lu, Hongbin Ji, Jingyi Hui |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | PLoS Genetics, Vol 10, Iss 4, p e1004289 (2014) |
| Druh dokumentu: | article |
| ISSN: | 1553-7390 1553-7404 |
| DOI: | 10.1371/journal.pgen.1004289 |
| Popis: | Lung cancer is the leading cause of cancer-related death worldwide. Aberrant splicing has been implicated in lung tumorigenesis. However, the functional links between splicing regulation and lung cancer are not well understood. Here we identify the RNA-binding protein QKI as a key regulator of alternative splicing in lung cancer. We show that QKI is frequently down-regulated in lung cancer, and its down-regulation is significantly associated with a poorer prognosis. QKI-5 inhibits the proliferation and transformation of lung cancer cells both in vitro and in vivo. Our results demonstrate that QKI-5 regulates the alternative splicing of NUMB via binding to two RNA elements in its pre-mRNA, which in turn suppresses cell proliferation and prevents the activation of the Notch signaling pathway. We further show that QKI-5 inhibits splicing by selectively competing with a core splicing factor SF1 for binding to the branchpoint sequence. Taken together, our data reveal QKI as a critical regulator of splicing in lung cancer and suggest a novel tumor suppression mechanism involving QKI-mediated regulation of the Notch signaling pathway. |
| Databáze: | Directory of Open Access Journals |
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