Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene
Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene
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DOI：
10.1038/sj.emboj.7601957
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发表时间：
2008-01-09
期刊：
影响因子：
11.4
通讯作者：
Conboy, John G.
中科院分区：
文献类型：
--
作者：
Parra, Marilyn K.;Tan, Jeff S.;Conboy, John G.
在蛋白4.1R基因中，备选第一外显子的剪接与远低于外显子2’/2 （E2’/2）的备选30个剪接位点的剪接不同。我们描述了一种新的剪接机制，通过外显子1B （E1B）的新特性调节的两个嵌套剪接反应，外显子1A （E1A）专门剪接到远端E2'/2受体。在第一步中，E1B表现为外显子，使用其共识50供体拼接到近端E2'/2受体。将下游的一长段内含子切除，将E1B与E2'/2并置于一起，生成一个新的复合受体，该受体包含E1B分支点/嘧啶束和E2远端30 ag -二核苷酸。接下来，上游的E1A通过E1B拼接到这个远端受体上，切除剩余的内含子加上E1B和E2’，形成成熟的E1A/E2产物。我们绘制了两个内剪接反应的分支点，并证明E1B 50剪接位点或分支点的突变会消除内剪接。在4.1R基因中，内剪接最终决定了n端蛋白的结构和功能。更一般地说，内剪接代表了一种新的机制，通过这种机制，备选启动子可以与下游备选剪接协调。
In the protein 4.1R gene, alternative first exons splice differentially to alternative 30 splice sites far downstream in exon 2'/2 (E2'/2). We describe a novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the distal E2'/2 acceptor via two nested splicing reactions regulated by novel properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its consensus 50 donor to splice to the proximal E2'/2 acceptor. A long region of downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal 30 AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2 product. We mapped branchpoints for both intrasplicing reactions and demonstrated that mutation of the E1B 50 splice site or branchpoint abrogates intrasplicing. In the 4.1R gene, intrasplicing ultimately determines N-terminal protein structure and function. More generally, intrasplicing represents a new mechanism by which alternative promoters can be coordinated with downstream alternative splicing.