Global profiling of alternative splicing events and gene expression regulated by hnRNPH/F.
Global profiling of alternative splicing events and gene expression regulated by hnRNPH/F.
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DOI：
10.1371/journal.pone.0051266
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cambi F
中科院分区：
文献类型：
--
作者：
Wang E;Aslanzadeh V;Papa F;Zhu H;de la Grange P;Cambi F
在这项研究中，我们已经调查了全球影响的异质核核糖核蛋白（hnRNP）H/F介导的剪接事件和基因表达的调节少突胶质细胞。我们已经在基因和外显子水平上对用靶向hnRNPH/F的siRNA处理的Oli-neu细胞进行了全基因组转录组学分析，并与未处理的细胞进行了比较。基因表达水平和调控外显子鉴定与基因剪接EASANA算法。进行生物信息学分析以确定与hnRNPH/F作为外显子包含的增强子与阻遏子的功能相关的G片段的结构特性。不同类型的选择性剪接事件由hnRNPH/F调节。内含子G束的密度、长度和与5′剪接位点的接近程度与hnRNPH/F增强子的功能相关。此外，6%的基因在敲低hnRNPH/F后不同地表达。调节少突胶质细胞祖细胞向少突胶质细胞转变的基因在hnRNPH/F耗尽的Oli-neu细胞中差异表达，导致负调节因子减少和分化诱导调节因子增加。这些变化在体内发育中的少突胶质细胞中得到证实。这是第一个全基因组分析剪接事件和基因表达的hnRNPH/F调节少突胶质细胞和第一份报告，hnRNPH/F调节基因参与从少突胶质细胞祖细胞的过渡少突胶质细胞。
In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events are regulated by hnRNPH/F. Intronic G tracts density, length and proximity to the 5′ splice site correlate with the hnRNPH/F enhancer function. Additionally, 6% of genes are differently expressed upon knock down of hnRNPH/F. Genes that regulate the transition of oligodendrocyte progenitor cells to oligodendrocytes are differentially expressed in hnRNPH/F depleted Oli-neu cells, resulting in a decrease of negative regulators and an increase of differentiation-inducing regulators. The changes were confirmed in developing oligodendrocytes in vivo. This is the first genome wide analysis of splicing events and gene expression regulated by hnRNPH/F in oligodendrocytes and the first report that hnRNPH/F regulate genes that are involved in the transition from oligodendrocyte progenitor cells to oligodendrocytes.
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