An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells.

An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells.
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DOI:
10.1038/nsmb.1545
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发表时间:
2009-02
影响因子:
16.8
通讯作者:
--
中科院分区:
生物学1区
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--
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阐明调控剪接的密码一直是理解转录后基因表达调控的一个长期目标,转录后基因表达对细胞的生存、分化和发育至关重要。我们通过在人类胚胎干细胞中通过交联式免疫沉淀和高通量测序(CLIP-SEQ)构建了细胞类型特异性剪接调节因子FOX2(也称为RBM9)的RNA图谱,在体内解码了功能RNA元件。该图谱确定了一大批特定的FOX2靶标,其中许多本身就是剪接调节子,将FOX2结合图谱与有效的剪接事件进行比较,揭示了FOX2调控的外显子以位置相关的方式包含或跳过的一般规则。这些发现表明FOX2是剪接网络的关键调节因子,我们进一步表明FOX2对人类胚胎干细胞的生存是重要的。
The elucidation of a code for regulated splicing has been a long-standing goal in understanding the control of post-transcriptional gene expression events that are crucial for cell survival, differentiation and development. We decoded functional RNA elements in vivo by constructing an RNA map for the cell type–specific splicing regulator FOX2 (also known as RBM9) via cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells. The map identified a large cohort of specific FOX2 targets, many of which are themselves splicing regulators, and comparison between the FOX2 binding profile and validated splicing events revealed a general rule for FOX2-regulated exon inclusion or skipping in a position-dependent manner. These findings suggest that FOX2 functions as a critical regulator of a splicing network, and we further show that FOX2 is important for the survival of human embryonic stem cells.
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