Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease
Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease
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DOI：
10.1002/ana.20107
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发表时间：
2004-05-01
影响因子：
11.2
通讯作者：
Ohno, S
中科院分区：
文献类型：
--
作者：
Usuki, F;Yamashita, A;Ohno, S
无义介导的mRNA衰变（NMD）是一种mRNA监视系统，其消除含有过早翻译终止密码子（PTC）的异常mRNA。我们评估了NMD在Ullrich病中的作用。该患者在胶原VI α 2基因中具有移码突变和PTC，导致胶原VI损失和细胞外基质（ECM）功能缺陷。NMD的药理学阻断引起突变型胶原VI α 2亚基的上调，导致胶原VI组装和部分功能性ECM形成。我们的研究结果表明，NMD抑制剂可以作为一种治疗工具，以挽救一些人类遗传疾病加剧的NMD。
Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance system that eliminates aberrant mRNAs containing premature translation termination codons (PTCs). We evaluated the role of NMD in of Ullrich's disease. The patient has a frameshift mutation with a PTC in the collagen VI alpha2 gene causing the loss of collagen VI and functional defects in extracellular matrix (ECM). The pharmacological block of NMD caused up-regulation of the mutant collagen VI alpha2 subunit, resulting in collagen VI assembly and partially functional ECM formation. Our results suggest that NMD inhibitors can be used as a therapeutic tool to rescue some human genetic diseases exacerbated by NMD.