Expansion of a CUG trinucleotide repeat in the 3' untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts
Expansion of a CUG trinucleotide repeat in the 3' untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts
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DOI：
10.1073/pnas.94.14.7388
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发表时间：
1997-07-08
影响因子：
11.1
通讯作者：
Housman, DE
中科院分区：
文献类型：
--
作者：
Davis, BM;McCurrach, ME;Housman, DE
在编码强直性肌营养不良蛋白激酶的基因DMPK的3'非翻译区（UTR）中CTG三核苷酸重复的扩增诱导显性遗传性神经肌肉疾病强直性肌营养不良（DM）。含有扩增的三核苷酸的转录物在分化的培养成肌细胞中是丰富的，并且它们被正常地剪接和聚腺苷酸化。然而，突变转录本永远不会到达这些非有丝分裂细胞的细胞质;相反，它们形成与核基质紧密相连的稳定簇，这可能会阻止这些转录本的有效生化纯化。在DM患者中，DMPK蛋白水平降低，随之而来的突变体转录物的核保留，可能是疾病发展的原因。核灶的形成是阻止转录本输出和影响基因功能丧失的一种新机制。
Expansion of a CTG trinucleotide repeat in the 3' untranslated region (UTR) of DMPK, the gene encoding myotonic dystrophy protein kinase, induces the dominantly inherited neuromuscular disorder myotonic dystrophy (DM). Transcripts containing the expanded trinucleotide are abundant in differentiated cultured myoblasts, and they are spliced and polyadenylylated normally. However, mutant transcripts never reach the cytoplasm in these nonmitotic cells; instead, they form stable clusters that are tightly linked to the nuclear matrix, which can prevent effective biochemical purification of these transcripts. In DM patients, reduced DMPK protein levels, consequent to nuclear retention of mutant transcripts, are probably a cause of disease development. Formation of nuclear foci is a novel mechanism for preventing transcript export and effecting a loss of gene function.