期刊
MOLECULAR CELL
卷 43, 期 3, 页码 353-368出版社
CELL PRESS
DOI: 10.1016/j.molcel.2011.05.035
关键词
-
资金
- EMBO
- HFSP
- Fundacion Marcelino Botin
- AICR
- Fundacion Alicia Koplowicz
- EURASNET
- Ministerio de Ciencia e Innovacion
- Consolider RNAREG
- ICREA Funding Source: Custom
The Ewing sarcoma (EWS) protein is a member of the TET (TLS/EWS/TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. We report that EWS depletion results in alternative splicing changes of genes involved in DNA repair and genotoxic stress signaling, including ABL1, CHEK2, and MAP4K2. Chromatin and RNA crosslinking immunoprecipitation results indicate that EWS cotranscriptionally binds to its target RNAs. This association is reduced upon irradiation of cells with ultraviolet light, concomitant with transient enrichment of EWS in nucleoli and with alternative splicing changes that parallel those induced by EWS depletion and that lead to reduced c-ABL protein expression. Consistent with the functional relevance of EWS-mediated alternative splicing regulation in DNA damage response, EWS depletion reduces cell viability and proliferation upon UV irradiation, effects that are attenuated by restoring c-ABL expression. These results provide insights into posttranscriptional mechanisms of DNA damage response by a TET protein.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据