首页> 外文期刊>Nucleic acids research >PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes
【24h】

PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes

机译:PLP / DM20比值由hnRNPH和F和少突胶质细胞中一种新型的富含G的增强剂调节

获取原文
获取外文期刊封面目录资料

摘要

Alternative splicing of competing 5′ splice sites is regulated by enhancers and silencers in the spliced exon. We have characterized sequences and splicing factors that regulate alternative splicing of PLP and DM20, myelin proteins produced by oligodendrocytes (OLs) by selection of 5′ splice sites in exon 3. We identify a G-rich enhancer (M2) of DM20 5′ splice site in exon 3B and show that individual G triplets forming M2 are functionally distinct and the distal group plays a dominant role. G-rich M2 and a G-rich splicing enhancer (ISE) in intron 3 share similarities in function and protein binding. The G-rich sequences are necessary for binding of hnRNPs to both enhancers. Reduction in hnRNPH and F expression in differentiated OLs correlates temporally with increased PLP/DM20 ratio. Knock down of hnRNPH increased PLP/DM20 ratio, while hnRNPF did not. Silencing hnRNPH and F increased the PLP/DM20 ratio more than hnRNPH alone, demonstrating a novel synergistic effect. Mutation of M2, but not ISE reduced the synergistic effect. Replacement of M2 and all G runs in exon 3B abolished it almost completely. We conclude that developmental changes in hnRNPH/F associated with OLs differentiation synergistically regulate PLP alternative splicing and a G-rich enhancer participates in the regulation.
机译:竞争性5'剪接位点的选择性剪接受剪接外显子中的增强子和沉默子调控。我们已经表征了序列和剪接因子,通过选择外显子3中的5'剪接位点来调节由少突胶质细胞(OL)产生的髓鞘蛋白PLP和DM20的选择性剪接。我们确定了DM20 5'剪接的富G增强子在第3B外显子​​的位点显示,形成M2的单个G三胞胎在功能上是不同的,远端组起主导作用。内含子3中富含G的M2和富含G的剪接增强子(ISE)在功能和蛋白质结合方面具有相似性。富含G的序列对于hnRNP与两种增强子的结合都是必需的。分化的OL中hnRNPH和F表达的降低与PLP / DM20比值的升高暂时相关。降低hnRNPH可以增加PLP / DM20的比率,而hnRNPF则没有。沉默hnRNPH和F比单独使用hnRNPH更能增加PLP / DM20的比率,表明了一种新的协同效应。 M2,但不是ISE的突变会降低协同效应。 M2和所有G在第3B外显子​​中的置换几乎完全消除了它。我们得出结论,与OLs分化相关的hnRNPH / F的发育变化可协同调节PLP选择性剪接,富含G的增强剂参与调节。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号