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RNA splicing mediated by YB‐1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells
Author(s) -
Rapp Timothy B.,
Yang Liu,
Conrad Ernest U.,
Mandahl Nils,
Chansky Howard A.
Publication year - 2002
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/s0736-0266(02)00006-2
Subject(s) - rna splicing , fusion protein , alternative splicing , biology , microbiology and biotechnology , myxoid liposarcoma , splicing factor , rna , gene isoform , chop , rna binding protein , rna polymerase ii , cancer research , liposarcoma , gene , genetics , sarcoma , endoplasmic reticulum , promoter , gene expression , recombinant dna , medicine , pathology
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. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.