RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells

Summary, in English

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 E1A 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. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

• Author: TB Rapp; L Yang; EU Conrad; Nils Mandahl; HA Chansky
• Department/s: Division of Clinical Genetics
• Publishing year: 2002
• Language: English
• Pages: 723-729
• Publication/Series: Journal of Orthopaedic Research
• Volume: 20
• Issue: 4
• Links: http://dx.doi.org/10.1016/S0736-0266(02)00006-2
• Document type: Journal article
• Publisher: John Wiley & Sons Inc.
• Topic: Orthopedics
• Keywords: RNA splicing; translocation; fusion protein; TLS/CHOP; sarcoma; YB-1
• Status: Published
• ISBN/ISSN/Other: ISSN: 1554-527X