The EWS/NOR1 Fusion Gene Product Gains a Novel Activity Affecting Pre-mRNA Splicing

Ohkura N, Yaguchi H, Tsukada T, Yamaguchi K

Journal of Biological Chemistry. 2001 Oct 22;277(1):535–43

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 thatEWS/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/NOR1caused increased usage of the distal 5′-splice site of pre-mRNA splicing and that EWS/NOR1 interacted with the human splicing protein U1C; neitherEWS nor NOR1 had the same activity or interaction as EWS/NOR1. Altogether, our findings reveal that EWS/NOR1 gains a novel activity affectingpre-mRNA splicing.