Control of alternative pre-mRNA splicing by distributed pentameric repeats
Control of alternative pre-mRNA splicing by distributed pentameric repeats
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DOI：
10.1073/pnas.94.23.12343
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发表时间：
1997-11-11
影响因子：
11.1
通讯作者：
Rosenfeld, MG
中科院分区：
文献类型：
--
作者：
Hedjran, F;Yeakley, JM;Rosenfeld, MG
六聚体TGCATG的多个拷贝已被证明可以调节纤维连接蛋白mrna前的选择性剪接，GCATG重复序列也聚集在大鼠降钙素/CGRP基因中受调节的降钙素特异性3'剪接位点附近，这些重复序列在降钙素/CGRP基因前mrna中的特异性突变导致降钙素特异性剪接的丢失，这表明天然重复序列增强了选择性外显子包含。这些元件亚群的突变表明，选择性剪接需要至少两个重复，并且一个内含子重复和一个外显子重复的组合是最佳细胞特异性剪接所必需的。然而，在野生型背景下和缺乏内源性重复的转录物中，多集化的内含子重复抑制了降钙素特异性剪接。这些结果表明，重复序列的数量和分布可能是组织特异性选择性剪接调控的重要特征。此外，含有单个重复序列的RNA结合细胞特异性蛋白复合物，但通过使用多聚合重复序列未检测到蛋白质结合的组织特异性差异。综上所述，这些数据支持了一个新的剪接调节模型，该模型需要细胞对多个分布序列元素的特异性识别。
Multiple copies of the hexamer TGCATG have been shown to regulate fibronectin pre-mRNA alternative splicing, GCATG repeats also are clustered near the regulated calcitonin-specific 3' splice site in the rat calcitonin/CGRP gene, Specific mutagenesis of these repeats in calcitonin/CGRP pre-mRNA resulted in the loss of calcitonin-specific splicing, suggesting that the native repeats act to enhance alternative exon inclusion, Mutation of subsets of these elements implies that alternative splicing requires a minimum of two repeats, and that the combination of one intronic and one exonic repeat is necessary for optimal cell-specific splicing, However, multimerized intronic repeats inhibited calcitonin-specific splicing in both the wild-type context and in a transcript lacking endogenous repeats. These results suggest that both the number and distribution of repeats may be important features for the regulation of tissue-specific alternative splicing, Further, RNA containing a single repeat bound cell-specific protein complexes, but tissue-specific differences in protein binding were not detected by using multimerized repeats. Together, these data support a novel model for alternative splicing regulation that requires the cell specific recognition of multiple, distributed sequence elements.