The pathological splicing mutation c.6792C>G in NF1 exon 37 causes a change of tenancy between antagonistic splicing factors

Abstract 

We have previously identified an ESE in NF1 exon 37 whose disruption by the pathological mutation c.6792C>G caused aberrant splicing. We now investigate the RNA-protein complexes affected by the c.6792C>G mutation observing that this concurrently decreases the affinity for the positive splicing factor YB-1 and increases the affinity for the negative splicing factors, hnRNPA1, hnRNPA2 and a new player in these type of complexes, DAZAP1. Our findings highlight the complexity of the interplay between positive and negative factors in the exon inclusion/skipping outcome. Furthermore, our observations stress the role of a wide genomic context in NF1 exon 37 definition.

Keywords: NF1, Exonic splicing enhancers, Exonic splicing silencers, YB-1, hnRNPA1, hnRNPA2, DAZAP1