The 185delAG mutation (c.68_ 69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon
The 185delAG mutation (c.68_ 69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon
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DOI：
10.1002/humu.20384
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发表时间：
2006-10-01
期刊：
影响因子：
3.9
通讯作者：
Mazoyer, Sylvie
中科院分区：
文献类型：
--
作者：
Buisson, Monique;Anczukow, Olga;Mazoyer, Sylvie
BRCA1基因中的185delAG突变（c.68_69delAG；ter39）是一种在德系犹太人群中具有奠基者效应的突变，该人群中有1%携带此突变，并且在数千名乳腺癌或卵巢癌患者中已被发现。我们先前已经描述过，带有这种突变的转录本，以及带有188del11突变（c.71 - 81del；ter36）的转录本，不会被无义介导的mRNA降解（NMD）所降解，这与我们对在编码序列更下游引入提前终止密码子（PTCs）的其他截短突变的观察结果相反[佩兰 - 维多兹等人，2002]。为了验证这两种突变由于翻译重新起始而未能触发NMD的假设，我们构建了BRCA1小基因，并研究了它们在HeLa细胞中瞬时表达后的蛋白质表达情况。我们在此表明，在第36或39位存在PTC的情况下，BRCA1小基因中的翻译重新起始发生在第128位。
The 185delAG mutation (c.68_69delAG; ter39) in the BRCA1 gene is a founder Jewish Ashkenazi mutation that is carried by 1% of this population and has been identified in thousands of breast or ovarian cancer patients. We have previously described that transcripts bearing this mutation, as well as transcripts bearing the 188del11 mutation (c.71-81del; ter36), are not degraded by nonsense-mediated mRNA decay (NMD), contrary to our observations of other truncating mutations that introduce premature termination codons (PTCs) farther downstream in the coding sequence [Perrin-Vidoz et al., 2002]. To test the hypothesis that these two mutations fail to trigger NMD because of translation reinitiation, we have constructed BRCA1 minigenes and studied their protein expression after transient expression in HeLa cells. We show here that in the presence of a PTC at position 36 or 39, translation reinitiation occurs in the BRCA1 minigenes at position 128.