RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells.
Human myxoid liposarcoma contains a characteristic t(12;16) chromosomal translocation that results in fusion of the N-terminal domain of the translocated in liposarcoma (TLS) protein to the C/EBP homologous protein (CHOP). TLS possesses structural motifs that suggest it may participate in RNA processing. We demonstrate that in human myxoid liposarcoma cells, wild-type TLS binds to RNA polymerase II (Pol II) via its N-terminal domain and to the transcription and translation factor Y-box binding protein-1 (YB-1) through its C-terminal domain. The liposarcoma fusion protein TLS/CHOP retains the ability to bind RNA Pol II but lacks the ability to recruit YB-1 due to replacement of the C-terminal domain of TLS by CHOP. In an in vivo splicing assay, YB-1 promotes splicing of adenovirus EIA pre-mRNA predominantly to the 13S isoform. The oncogenic TLS/CHOP fusion protein inhibits this splicing function of YB-1 in a dominant negative manner. When considered in conjunction with studies on other sarcoma fusion proteins, these data suggest that aberrant RNA splicing may be a common feature of human sarcomas.
Rapp
Timothy B
TB
Department of Orthopaedics and Sports Medicine, School of Medicine, University of Washington, Seattle 98108, USA.
Yang
Liu
L
Conrad
Ernest U
EU
Mandahl
Nils
N
Chansky
Howard A
HA
D017500:Adenovirus E1A Proteins / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D018208:Liposarcoma, Myxoid / Q000235:genetics*; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D012319:RNA Polymerase II / Q000378:metabolism; D012326:RNA Splicing; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins / Q000737:chemistry / Q000502:physiology; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D051840:Y-Box-Binding Protein 1
D017500:Adenovirus E1A Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; C106030:TLS-CHOP fusion protein, human; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D051742:Transcription Factor CHOP; D012319:RNA Polymerase II