| Literature DB >> 26776507 |
Patrick J Grohar1, Suntae Kim2, Guillermo O Rangel Rivera3, Nirmalya Sen2, Sara Haddock2, Matt L Harlow4, Nichole K Maloney5, Jack Zhu6, Maura O'Neill7, Tamara L Jones2, Konrad Huppi2, Magdalena Grandin2, Kristen Gehlhaus2, Carleen A Klumpp-Thomas8, Eugen Buehler8, Lee J Helman9, Scott E Martin8, Natasha J Caplen10.
Abstract
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-FLI1 pre-mRNA. We show that Ewing sarcoma cells harboring a genomic breakpoint that retains exon 8 of EWSR1 require the RNA-binding protein HNRNPH1 to express in-frame EWS-FLI1. We also demonstrate the sensitivity of EWS-FLI1 fusion transcripts to the loss of function of the U2 snRNP component, SF3B1. Disrupted splicing of the EWS-FLI1 transcript alters EWS-FLI1 protein expression and EWS-FLI1-driven expression. Our results show that the processing of the EWS-FLI1 fusion RNA is a potentially targetable vulnerability in Ewing sarcoma cells.Entities:
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Year: 2016 PMID： 26776507 PMCID： PMC4755295 DOI： 10.1016/j.celrep.2015.12.063
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423