Concentration dependent selection of targets by an SR splicing regulator results in tissue-specific RNA processing.
Concentration dependent selection of targets by an SR splicing regulator results in tissue-specific RNA processing.
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DOI：
10.1093/nar/gkl755
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发表时间：
2006
影响因子：
14.9
通讯作者：
Mattox W
中科院分区：
文献类型：
--
作者：
Qi J;Su S;McGuffin ME;Mattox W
剪接因子Transformer-2（Tra 2）在果蝇成虫中几乎普遍表达，但参与几种RNA剪接的组织特异性调节。在体细胞组织中，Tra 2参与doubletex和fruitless pre-mRNA中性别特异性剪接位点的激活。在雄性生殖系中，它影响其他转录本的剪接，并抑制M1内含子从其自身前mRNA中的去除。在这里，我们测试的假设，M1抑制的种系特异性是由Tra 2浓度的组织特异性差异。我们发现Tra 2在男性初级精母细胞中的表达水平高于其他细胞类型。其他组织中Tra 2表达的增加以与雄性生殖系中Tra 2过度表达的已知剂量依赖性效应一致的方式降低活力。体细胞被认为是有能力抑制M1剪接，如果Tra 2转录水平高于内源性浓度。这表明，不仅M1的抑制是限制在生殖细胞的Tra 2转录水平的差异，但也表明，蛋白质的阈值浓度M1的调节不同于doubletex和无结果的RNA。我们建议，调节表达的定量差异可以引起细胞类型特异性限制剪接。
The splicing factor Transformer-2 (Tra2) is expressed almost ubiquitously in Drosophila adults, but participates in the tissue-specific regulation of splicing in several RNAs. In somatic tissues Tra2 participates in the activation of sex-specific splice sites in doublesex and fruitless pre-mRNAs. In the male germline it affects splicing of other transcripts and represses removal of the M1 intron from its own pre-mRNA. Here we test the hypothesis that the germline specificity of M1 repression is determined by tissue-specific differences in Tra2 concentration. We find that Tra2 is expressed at higher levels in primary spermatocytes of males than in other cell types. Increased Tra2 expression in other tissues reduces viability in a manner consistent with known dose-dependent effects of excessive Tra2 expression in the male germline. Somatic cells were found to be competent to repress M1 splicing if the level of Tra2 transcription was raised above endogenous concentrations. This suggests not only that M1 repression is restricted to the germline by a difference in Tra2 transcription levels but also that the protein's threshold concentration for M1 regulation differs from that of doublesex and fruitless RNAs. We propose that quantitative differences in regulator expression can give rise to cell-type-specific restrictions in splicing.
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影响因子：
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通讯作者：
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