The efficiency of nonsense-mediated mRNA decay is an inherent character and varies among different cells
The efficiency of nonsense-mediated mRNA decay is an inherent character and varies among different cells
复制标题
DOI：
10.1038/sj.ejhg.5201889
复制
发表时间：
2007-11-01
影响因子：
5.2
通讯作者：
Kerem, Batsheva
中科院分区：
文献类型：
--
作者：
Linde, Liat;Boelz, Stephanie;Kerem, Batsheva
无意义介导的信使核糖核酸衰变(NMD)是一种选择性地降解携带提前终止密码子(PTCs)的转录本和含有NMD诱导特征的各种生理转录本的机制。在最近的一项研究中，我们发现囊性纤维化(CF)患者的鼻黏膜上皮细胞的NMD效率不同。携带W1282X PTC的CF跨膜电导调节因子(CFTR)转录本以及几种NMD生理底物都存在这种可变性。在这里，我们的目的是调查NMD效率的变异性是一种更普遍的现象的可能性，并不局限于鼻腔上皮细胞。为了研究这种可能性，我们分析了携带W1282X PTC的CFTR构建体和携带NS39 PTC的β-珠蛋白构建体在HeLa和MCF7细胞中的NMD效率。两个细胞之间的NMD效率存在差异，因此在HeLa细胞中NMD效率很高，而在MCF7细胞中NMD效率显著较低。此外，在5个内源NMD生理转录本中也发现了类似的NMD效率差异。总之，我们的结果证明了细胞的存在，在这些细胞中，所有转录本的NMD是有效的，而在其他细胞中，NMD的效率较低，这表明NMD的效率是细胞的固有特征。我们的结果还表明，NMD疗效的变异性是一种普遍现象，并不局限于鼻腔上皮细胞。由于NMD影响许多转录本的水平，NMD效率的变异性可能作为不同细胞功能的遗传修饰物发挥作用。
Nonsense-mediated mRNA decay (NMD) is a mechanism, which selectively degrades transcripts carrying premature termination codons (PTCs) and a variety of physiologic transcripts containing NMD-inducing features. In a recent study, we have found variable NMD efficiency among nasal epithelial cells obtained from cystic fibrosis (CF) patients. This variability was found for CF transmembrane conductance regulator (CFTR) transcripts carrying the W1282X PTC, as well as for several NMD physiologic substrates. Here, we aimed to investigate the possibility that variability in NMD efficiency is a more generalized phenomenon and is not restricted to nasal epithelial cells. To investigate this possibility, we analyzed the NMD efficiency of both a CFTR constructs carrying the W1282X PTC and beta-globin constructs carrying the NS39 PTC, in HeLa and MCF7 cells. Variability in NMD efficiency was found for both constructs between the cells, such that in HeLa cells the NMD was highly efficient and in MCF7 the efficiency was significantly lower. Moreover, similar differences in the efficiency of NMD were found for five endogenous NMD physiologic transcripts. Altogether, our results demonstrate existence of cells in which NMD of all transcripts is efficient, whereas others in which the NMD is less efficient, suggesting that the efficiency of NMD is an inherent character of cells. Our results also suggest that variability in the efficiency of NMD is a general phenomenon and is not restricted to nasal epithelial cells. As NMD affects the level of many transcripts, variability in the NMD efficiency might play a role as a genetic modifier of different cellular functions.