The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing.

Abstract	In extraskeletal myxoid chondrosarcoma, chromosomal translocation creates a gene fusion between EWS and the orphan nuclear receptor NOR1. The resulting fusion gene product, EWS/NOR1, has been believed to lead to malignant transformation by functioning as a transcriptional activator, but an alternative mechanism may also be involved. Here, using a newly developed functional complementation screening in yeast, we found that EWS/NOR1, but not EWS or NOR1, complemented the loss of function of the small nuclear ribonucleoprotein Snu23p, an essential factor for pre-mRNA splicing in yeast. To verify the potential function of EWS/NOR1 in mammalian cells, we next showed that overexpression of EWS/NOR1 caused increased usage of the distal 5'-splice site of pre-mRNA splicing and that EWS/NOR1 interacted with the human splicing protein U1C; neither EWS nor NOR1 had the same activity or interaction as EWS/NOR1. Altogether, our findings reveal that EWS/NOR1 gains a novel activity affecting pre-mRNA splicing.
Authors	Naganari Ohkura, Hiroko Yaguchi, Toshihiko Tsukada, Ken Yamaguchi
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 1 Pg. 535-43 (Jan 04 2002) ISSN: 0021-9258 [Print] United States
PMID	11673470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adenovirus E1A Proteins DNA-Binding Proteins Heterogeneous-Nuclear Ribonucleoproteins NR4A3 protein, human Nerve Tissue Proteins Nr4a3 protein, mouse RNA Precursors RNA-Binding Protein EWS Receptors, Steroid Receptors, Thyroid Hormone Recombinant Fusion Proteins Ribonucleoproteins Ribonucleoproteins, Small Nuclear SNRPC protein, human
Topics	Adenovirus E1A Proteins (genetics) Amino Acid Sequence Animals Cell Nucleus (chemistry) DNA-Binding Proteins (analysis, physiology) Heterogeneous-Nuclear Ribonucleoproteins Humans Molecular Sequence Data Nerve Tissue Proteins (analysis, physiology) RNA Precursors (genetics) RNA Splicing RNA-Binding Protein EWS Receptors, Steroid Receptors, Thyroid Hormone Recombinant Fusion Proteins (analysis, physiology) Ribonucleoproteins (analysis, physiology) Ribonucleoproteins, Small Nuclear (metabolism)

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