Skoko Natasa, Baralle Marco, Buratti Emanuele, Baralle Francisco E
International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, Trieste, Italy.
FEBS Lett. 2008 Jun 25;582(15):2231-6. doi: 10.1016/j.febslet.2008.05.018. Epub 2008 May 27.
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.
我们之前在NF1基因第37外显子中鉴定出一个外显子剪接增强子（ESE），其被病理性突变c.6792C>G破坏后导致异常剪接。我们现在研究受c.6792C>G突变影响的RNA-蛋白质复合物，观察到该突变同时降低了对正向剪接因子YB-1的亲和力，并增加了对负向剪接因子hnRNPA1、hnRNPA2以及这类复合物中的一个新成员DAZAP1的亲和力。我们的研究结果突出了正向和负向因子在外显子包含/跳跃结果中相互作用的复杂性。此外，我们的观察结果强调了广泛的基因组背景在NF1基因第37外显子界定中的作用。
