Inhibition of specific gene expressions by protein-mediated mRNA interference
Inhibition of specific gene expressions by protein-mediated mRNA interference
复制标题
DOI：
10.1038/ncomms1621
复制
发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Inouye, Masayori
中科院分区：
文献类型：
--
作者：
Yamaguchi, Yoshihiro;Nariya, Hirofumi;Inouye, Masayori
由RNA介导的RNA干扰（如反义RNA、短干扰RNA和微小RNA）在信使RNA水平上调节特定基因的表达。然而，由蛋白质介导的RNA干扰尚未报道。在这里，我们确定MazF-hw mRNA干扰酶从一个超嗜盐古菌，在一个特定的七个碱基序列（UUACUCA）切割RNA。发现该序列在古细菌的视紫红质转录激活因子和一些膜蛋白的mRNA中异常丰富，这表明这些蛋白的表达受MazF-hw调节。当大肠杆菌中必需基因中的所有七个碱基切割位点被消除时，细胞不再对MazF-hw敏感，这表明特异性基因表达可以由序列特异性mRNA干扰酶调节。这些发现表明，mRNA干扰不仅可以由RNA介导，也可以由蛋白质介导，以有效地沉默细胞中的特定基因表达。
RNA interference mediated by RNA such as antisense RNA, short interfering RNA and micro RNA is well documented to regulate specific gene expression at the level of messenger RNA. However, RNA interference mediated by proteins has not been reported. Here we identify the MazF-hw mRNA interferase from a superhalophilic archaeon that cleaves RNA at a specific seven-base sequence (UUACUCA). This sequence was found unusually abundant in the mRNAs for rhodopsin transcription activator and some membrane proteins of the archaeon, suggesting that the expression of these proteins is regulated by MazF-hw. When all of the seven-base cleavage sites in essential genes in Escherichia coli were eliminated, the cells were no longer sensitive to MazF-hw, demonstrating that specific gene expression can be regulated by a sequence-specific mRNA interferase. These findings demonstrate that mRNA interference can be mediated not only by RNA but also by proteins to effectively silence specific gene expression in cells.