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J Biol Chem, Vol. 273, Issue 43, 27761-27764, October 23, 1998

COMMUNICATION
Oncoprotein TLS Interacts with Serine-Arginine Proteins Involved in RNA Splicing

Liu YangDagger §, Lisa J. EmbreeDagger §, Schickwann Tsai, and Dennis D. HicksteinDagger §parallel

From the Dagger  Medical Research Service, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108,  Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, and § Division of Oncology and parallel  Molecular Medicine, University of Washington School of Medicine, Seattle, Washington 98195

The gene encoding the human TLS protein, also termed FUS, is located at the site of chromosomal translocations in human leukemias and sarcomas where it forms a chimeric fusion gene with one of several different genes. To identify interacting partners of TLS, we screened a yeast two-hybrid cDNA library constructed from mouse hematopoietic cells using the C-terminal region of TLS in the bait plasmid. Two cDNAs encoding members of the serine-arginine (SR) family of proteins were isolated. The first SR protein is the mouse homolog of human splicing factor SC35, and the second SR member is a novel 183-amino acid protein that we term TASR (TLS-associated serine-arginine protein). cDNA cloning of human TASR indicated that mouse and human TASR have identical amino acid sequences. The interactions between TLS and these two SR proteins were confirmed by co-transfection and immunoprecipitation studies. In vivo splicing assays indicated that SC35 and TASR influence splice site selection of adenovirus E1A pre-mRNA. TLS may recruit SR splicing factors to specific target genes through interaction with its C-terminal region, and chromosomal translocations that truncate the C-terminal region of TLS may prevent this interaction. Thus TLS translocations may alter RNA processing and play a role in malignant transformation.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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