Co-transcriptional commitment to alternative splice site selection

Co-transcriptional commitment to alternative splice site selection
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DOI:
10.1093/nar/26.24.5568
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发表时间:
1998-12-15
影响因子:
14.9
通讯作者:
Smith, CWJ
Smith, CWJ
中科院分区:
生物学2区
文献类型:
--
作者:
Roberts, GC;Gooding, C;Smith, CWJ

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真核细胞中mRNA的产生不仅涉及转录,还涉及各种加工反应,如剪接。最近的实验表明,转录和加工机制的组件之间存在直接的物理联系,支持先前的建议,即前mRNA剪接发生共转录。在这里,我们使用了一种新的功能性方法来证明选择性剪接的共转录调控。α-原肌球蛋白基因的外显子3在平滑肌细胞中被特异性抑制。通过延迟一个重要的下游抑制元件的合成,我们表明,剪接或抑制外显子3的决定发生在有限的机会窗口转录后,表明剪接位点的选择迅速进行转录后。
Production of mRNA in eukaryotic cells involves not only transcription but also various processing reactions such as splicing. Recent experiments have indicated that there are direct physical connections between components of the transcription and processing machinery, supporting previous suggestions that pre-mRNA splicing occurs co-transcriptionally. Here we have used a novel functional approach to demonstrate co-transcriptional regulation of alternative splicing. Exon 3 of the alpha-tropomyosin gene is specifically repressed in smooth muscle cells. By delaying synthesis of an essential downstream inhibitory element, we show that the decision to splice or repress exon 3 occurs during a limited window of opportunity following transcription, indicating that splice site selection proceeds rapidly after transcription.