Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells
Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells
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DOI：
10.1093/hmg/11.7.805
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发表时间：
2002-04-01
影响因子：
3.5
通讯作者：
Brook, JD
中科院分区：
文献类型：
--
作者：
Fardaei, M;Rogers, MT;Brook, JD
强直性肌营养不良是一种复杂的神经肌肉疾病，与两个不同基因的DNA扩增突变有关。在DM1中，DMPK 3‘-非翻译区的CTG重复序列被扩增，而在DM2中，内含子CCTG扩增发生在基因ZNF9中。含有扩展重复序列的转录本在DM1和DM2细胞的细胞核中形成焦点。最近使用抗体的研究表明，与果蝇肌肉盲相关的蛋白质与DM1和DM2细胞中的重复焦点共存。我们发现，不是有一个人类盲肌基因通过选择性剪接产生多个蛋白质，事实上有三个不同的盲肌基因，MBNL，MBLL和MBXL，分别映射到染色体3，13和X，并显示出广泛的选择性剪接。其中两个基因，MBNL和MBLL，在许多成人组织中表达，而MBXL主要在胎盘中表达。绿色荧光蛋白标记的MBNL、MBLL和MBXL在DM1和DM2细胞中与核病灶共定位，提示这三种蛋白都可能在DM的病理生理过程中发挥作用。
Myotonic dystrophy is a complex neuromuscular disorder associated with DNA expansion mutations in two different genes. In DM1 a CTG repeat in the 3'-untranslated region of DMPK is expanded, whereas in DM2 an intronic CCTG expansion occurs in the gene ZNF9. Transcripts containing expanded repeats form foci in the nuclei of DM1 and DM2 cells. Recent work using antibodies has shown that proteins related to Drosophila muscleblind co-localize with repeat foci in DM1 and DM2 cells. We show that rather than there being a single human muscleblind gene producing multiple proteins through alternative splicing, there are in fact three different muscleblind genes, MBNL, MBLL and MBXL, which map to chromosomes 3, 13 and X, respectively, and which show extensive alternative splicing. Two of the genes, MBNL and MBLL, are expressed in many adult tissues whereas MBXL is expressed predominantly in the placenta. Green fluorescent protein-tagged versions of MBNL, MBLL and MBXL co-localize with nuclear foci in DM1 and DM2 cells, suggesting that all three proteins may play a role in DM pathophysiology.