Multiple interdependent sequence elements control splicing of a fibroblast growth factor receptor 2 alternative exon
Multiple interdependent sequence elements control splicing of a fibroblast growth factor receptor 2 alternative exon
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DOI：
10.1128/mcb.17.9.5106
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发表时间：
1997-09-01
影响因子：
5.3
通讯作者：
Breathnach, R
中科院分区：
文献类型：
--
作者：
DelGatto, F;Plet, A;Breathnach, R
成纤维细胞生长因子受体2基因包含一对互斥的外显子，其中一个（K-SAM）在上皮细胞中特异性剪接，Wet先前已经描述过（F. Del Gatto和R. Breathnach, Mol. Cell）。Biol. 15:4825-4834, 1995)一些控制K-SAM外显子剪接的元件，即well；外显子剪接位点，外显子抑制序列和内含子激活序列，我们在这里确定了K-SAM外显子下游的内含子中激活外显子剪接的另外两个序列。第一个序列（内含子激活序列2 [IAS2]）位于前on的5'剪接位点下游168 - 186个核苷酸处。第二个序列（内含子激活序列3 [IAS3]）位于外显子5'剪接位点下游的933至1052个核苷酸处。IAS3是一个由多个dart组成的复杂区域，其中一个（核苷酸963 ~ 983）可能与IAS2形成RNA二级结构。该结构由两个由不对称凸起分开的茎组成，突变破坏其中一个茎会减少激活，而重建茎的补偿突变会完全或部分地恢复激活，这取决于突变。我们提出了一个涉及多个相互依赖的pre-mRNA序列元素干预的K-SAM外显子剪接模型。
The fibroblast growth factor receptor 2 gene contains a pair of mutually exclusive alternative exons, one of which (K-SAM) is spliced specifically in epithelial cells, Wet have described previously (F. Del Gatto and R. Breathnach, Mol. Cell. Biol. 15:4825-4834, 1995) some elements controlling K-SAM exon splicing, namely weal; exon splice sites, an exon-repressing sequence, and an intron-activating sequence, We identify here two additional sequences in the intron downstream from the K-SAM exon which activate splicing of the exon. The first sequence (intron-activating sequence 2 [IAS2]) lies 168 to 186 nucleotides downstream from the ex-on's 5' splice site. The second sequence (intron-activating sequence 3 [IAS3]) lies 933 to 1,052 nucleotides downstream from the exon's 5' splice site. IAS3 is a complex region composed of several Darts, one of which (nucleotides 963 to 983) can potentially form an RNA secondary structure with IAS2. This structure is composed of two stems separated by an asymmetric bulge, Mutations which disrupt either stem decrease activation, while compensatory mutations which reestablish the stem restore activation, either completely or partially, depending on the mutation, We present a model for K-SAM exon splicing involving the intervention of multiple, interdependent pre-mRNA sequence elements.