التفاصيل البيبلوغرافية
| العنوان: |
Functional Genomic Screening Reveals Splicing of the EWS-FLI1Fusion Transcript as a Vulnerability in Ewing Sarcoma |
| المؤلفون: |
Grohar, Patrick J., Kim, Suntae, Rangel Rivera, Guillermo O., Sen, Nirmalya, Haddock, Sara, Harlow, Matt L., Maloney, Nichole K., Zhu, Jack, O’Neill, Maura, Jones, Tamara L., Huppi, Konrad, Grandin, Magdalena, Gehlhaus, Kristen, Klumpp-Thomas, Carleen A., Buehler, Eugen, Helman, Lee J., Martin, Scott E., Caplen, Natasha J. |
| المصدر: |
Cell Reports; January 2016, Vol. 14 Issue: 3 p598-610, 13p |
| مستخلص: |
Ewing sarcoma cells depend on the EWS-FLI1 fusion transcription factor for cell survival. Using an assay of EWS-FLI1 activity and genome-wide RNAi screening, we have identified proteins required for the processing of the EWS-FLI1pre-mRNA. We show that Ewing sarcoma cells harboring a genomic breakpoint that retains exon 8 of EWSR1require the RNA-binding protein HNRNPH1 to express in-frame EWS-FLI1. We also demonstrate the sensitivity of EWS-FLI1fusion transcripts to the loss of function of the U2 snRNP component, SF3B1. Disrupted splicing of the EWS-FLI1transcript alters EWS-FLI1 protein expression and EWS-FLI1-driven expression. Our results show that the processing of the EWS-FLI1fusion RNA is a potentially targetable vulnerability in Ewing sarcoma cells. |
| قاعدة البيانات: |
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