Reference: Ohkura N, et al. (2002) The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing. J Biol Chem 277(1):535-43

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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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Ohkura N, Yaguchi H, Tsukada T, Yamaguchi K
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