Infrequent translation of a nonsense codon is sufficient to decrease mRNA level

被引:25
作者
Buzina, A
Shulman, MJ [1 ]
机构
[1] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada
关键词
D O I
10.1091/mbc.10.3.515
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In many organisms nonsense mutations decrease the level of mRNA. In the case of mammalian cells, it is still controversial whether translation is required for this nonsense-mediated RNA decrease (NMD). Although previous analyzes have shown that conditions that impede translation termination at nonsense codons also prevent NMD, the residual level of termination was unknown in these experiments. Moreover, the conditions used to impede termination might also have interfered with NMD in other ways. Because of these uncertainties, we have tested the effects of limiting translation of a nonsense codon in a different way, using two mutations in the immunoglobulin mu heavy chain gene. For this purpose we exploited an exceptional nonsense mutation at codon 3, which efficiently terminates translation but nonetheless maintains a high level of mu mRNA. We have shown 1) that translation of Ter462 in the double mutant occurs at only similar to 4% the normal frequency, and 2) that Ter462 in cis with Ter3 can induce NMD. That is, translation of Ter462 at this low (4%) frequency is sufficient to induce NMD.
引用
收藏
页码:515 / 524
页数:10
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