PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes.
PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes.
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DOI：
10.1093/nar/gkm387
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发表时间：
2007
影响因子：
14.9
通讯作者：
Cambi F
中科院分区：
文献类型：
--
作者：
Wang E;Dimova N;Cambi F
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的调控。我们已经鉴定了调控PLP和DM 20选择性剪接的序列和剪接因子，这些蛋白是由少突胶质细胞（OL）通过选择外显子3中的5′剪接位点产生的。我们在DM 20外显子3B的5′剪接位点上发现了一个富含G的增强子（M2），并表明形成M2的单个G三联体在功能上是不同的，远端组起主导作用。富含G的M2和内含子3中的富含G的剪接增强子（伊势）在功能和蛋白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是必需的。hnRNPH和F在分化的OL中表达的减少与PLP/DM 20比率的增加暂时相关。hnRNPH的敲低增加PLP/DM 20比值，而hnRNPF没有。沉默hnRNPH和F增加PLP/DM 20比超过单独的hnRNPH，证明了一种新的协同效应。M2的突变而非伊势的突变降低了协同效应。替换M2和外显子3B中的所有G运行几乎完全消除了它。我们的结论是，与OLs分化相关的hnRNPH/F的发育变化协同调节PLP选择性剪接，富含G的增强子参与调节。
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.
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影响因子：
4.8
作者：
Garneau, D;Revil, T;Chabot, B
通讯作者：
Chabot, B
影响因子：
2.6
作者：
Liu, JH;Beqaj, S;Schuger, L
通讯作者：
Schuger, L
DOI：
10.1073/pnas.84.16.5665
发表时间：
1987-08-01
影响因子：
11.1
作者：
NAVE, KA;LAI, C;MILNER, RJ
通讯作者：
MILNER, RJ
影响因子：
5.3
作者：
Elrick, LL;Humphrey, MB;Berget, SM
通讯作者：
Berget, SM
影响因子：
14.9
作者：
MATUNIS, MJ;XING, J;DREYFUSS, G
通讯作者：
DREYFUSS, G