首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Brain-specific change in alternative splicing of Tau exon 6 in myotonic dystrophy type 1
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Brain-specific change in alternative splicing of Tau exon 6 in myotonic dystrophy type 1

机译:1型强直性肌营养不良症中Tau外显子6选择性剪接的大脑特异性变化

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Alternative splicing is altered in myotonic dystrophy of type 1 (DM1), a syndrome caused by an increase of CTG triplet repeats in the 3' untranslated region of the in myotonic dystrophy protein kinase gene. Previously, we reported the preferential skipping of Tau exon 2 in DM1 brains. In this study, we analyze the alternative splicing of Tau exon 6 which can be inserted in three different forms (c, p and d) depending on the 3' splice site used. In fact, inclusion of exon 6c decreases in DM1 brains compared to control brains whereas inclusion of 6d increases. Alteration of exon 6 splicing was not observed in DM1 muscle although this exon was inserted in RNAs from normal muscle and DM1 splicing alterations were first described in this organ. In contrast, alteration of exon 2 of Tau mRNA was observed in both muscle and brain. However, co-transfections of a minigene containing exon 6 with CELF or MBNL1 cDNAs, two splicing factor families suspected to be involved in DM1, showed that they influence exon 6 splicing. Altogether, these results show the importance of determining all the exons and organs targeted by mis-splicing to determine the dysregulation mechanisms of mis-splicing in DM1.
机译:1型强直性肌营养不良症(DM1)是由强直性肌营养不良蛋白激酶基因3'非翻译区CTG三联体重复增加引起的综合症,其替代的剪接发生了改变。先前,我们报道了DM1大脑中Tau外显子2的优先跳过。在这项研究中,我们分析了Tau外显子6的可变剪接,它可以根据所使用的3'剪接位点以三种不同的形式(c,p和d)插入。实际上,与对照组相比,DM1大脑中外显子6c的包含减少,而6d包含物的增加。尽管该外显子已插入正常肌肉的RNA中,但在DM1肌肉中未观察到外显子6剪接的改变,并且首先在该器官中描述了DM1剪接的改变。相反,在肌肉和大脑中都观察到Tau mRNA外显子2的改变。但是,含有外显子6的小基因与CELF或MBNL1 cDNA(怀疑是DM1的两个剪接因子家族)的共转染显示它们影响外显子6剪接。总而言之,这些结果表明确定所有通过错误剪接而确定的外显子和器官的重要性,以确定DM1中错误剪接的失调机制。

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