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.
Mesh Terms:
Adenovirus E1A Proteins, CCAAT-Enhancer-Binding Proteins, DNA-Binding Proteins, Heterogeneous-Nuclear Ribonucleoproteins, Humans, Liposarcoma, Myxoid, NFI Transcription Factors, Nuclear Proteins, Oncogene Proteins, Fusion, RNA Polymerase II, RNA Splicing, RNA-Binding Protein FUS, Ribonucleoproteins, Transcription Factor CHOP, Transcription Factors, Tumor Cells, Cultured, Y-Box-Binding Protein 1
J. Orthop. Res.
Date: Jul. 01, 2002
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