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

Rapp, TB; Yang, L; Conrad, EU; Mandahl, Nils LU and Chansky, HA (2002) In Journal of Orthopaedic Research 20(4). p.723-729
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
RNA splicing, translocation, fusion protein, TLS/CHOP, sarcoma, YB-1
in
Journal of Orthopaedic Research
volume
20
issue
4
pages
723 - 729
publisher
John Wiley & Sons
external identifiers
  • wos:000177191600012
  • pmid:12168660
  • scopus:0036319256
ISSN
1554-527X
DOI
10.1016/S0736-0266(02)00006-2
language
English
LU publication?
yes
id
f738e7ea-2957-4249-9a0e-3160e9eaf47e (old id 331972)
date added to LUP
2007-11-09 14:13:33
date last changed
2017-01-01 04:40:20
@article{f738e7ea-2957-4249-9a0e-3160e9eaf47e,
  abstract     = {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       = {Rapp, TB and Yang, L and Conrad, EU and Mandahl, Nils and Chansky, HA},
  issn         = {1554-527X},
  keyword      = {RNA splicing,translocation,fusion protein,TLS/CHOP,sarcoma,YB-1},
  language     = {eng},
  number       = {4},
  pages        = {723--729},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Orthopaedic Research},
  title        = {RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells},
  url          = {http://dx.doi.org/10.1016/S0736-0266(02)00006-2},
  volume       = {20},
  year         = {2002},
}