Serine/arginine-rich protein-dependent suppression of exon skipping by exonic splicing enhancers
Serine/arginine-rich protein-dependent suppression of exon skipping by exonic splicing enhancers
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DOI：
10.1073/pnas.0500543102
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发表时间：
2005-04-05
影响因子：
11.1
通讯作者：
Maniatis, T
中科院分区：
文献类型：
--
作者：
Ibrahim, EC;Schaal, TD;Maniatis, T
原则上，一个内含子中的5‘和3’剪接点可以在前mRNA剪接过程中与任何其他内含子中的剪接点连接。然而，在结构性剪接的前mRNAs中，外显子以严格的5‘到3’线性顺序连接。因此，必须存在特定的机制来防止外显子的随机连接。在此，我们报道了将外显子序列插入内含子可以抑制下游3‘剪接位点的剪接，并且这种抑制与内含子大小无关。剪接抑制所需的外显子序列被发现是外显子增强元件，它们的抑制活性需要富含丝氨酸/精氨酸的剪接因子的结合。我们认为，外显子增强子可以作为屏障来防止外显子跳跃，从而在确保剪接的mRNA中正确的外显子5‘到3’线性顺序中发挥关键作用。
The 5' and 3' splice sites within an intron can, in principle, be joined to those within any other intron during pre-mRNA splicing. However, exons are joined in a strict 5' to 3' linear order in constitutively spliced pre-mRNAs. Thus, specific mechanisms must exist to prevent the random joining of exons. Here we report that insertion of exon sequences into an intron can inhibit splicing to the downstream 3' splice site and that this inhibition is independent of intron size. The exon sequences required for splicing inhibition were found to be exonic enhancer elements, and their inhibitory activity requires the binding of serine/arginine-rich splicing factors. We conclude that exonic enhancers can act as barriers to prevent exon skipping and thereby may play a key role in ensuring the correct 5' to 3' linear order of exons in spliced mRNA.