1月3日，国际著名杂志自然-通讯Nature Communications在线刊登了美国和日本的研究人员的最新研究成果“Inhibition of specific gene expressions by protein-mediated mRNA interference。”，文章中，作者报道了一种新的抑制基因表达的方法，作者运用蛋白质介导的RNA干扰的方法从而来抑制特定基因的表达。
RNAi(RNA interference)即指的是与靶基因同源的双链RNA诱导的特异转录后基因沉默表达的一种现象，RNAi的作用机理是核酸内切酶Dicer将dsRNA（双链RNA）切割成多个具有特定长度和结构的小片段RNA即siRNA，siRNA在细胞内RNA解旋酶的作用下解链成正义链和反义链，然后反义siRNA再与体内一些酶结合形成RNA诱导的沉默复合物(RNA-induced silencing complex，RISC)。RISC与外源性基因表达的mRNA的同源区进行特异性结合并且在结合部位切割mRNA，被切割后的断裂mRNA随即降解。siRNA不仅能引导RISC切割同源单链mRNA，而且可作为引物与靶RNA结合并在RNA聚合酶(RNA-dependent RNA polymerase，RdRP)作用下合成更多新的dsRNA，新合成的dsRNA再由Dicer切割产生大量的次级siRNA，从而使RNAi的作用进一步放大，最终将靶mRNA完全降解。如今RNA干扰技术已经发展成为基因治疗、基因结构功能研究的快速而有效的方法。
在文章中，研究人员首次报道了运用蛋白质介导的RNA干扰的方法，一把情况下，RNAi涉及的RNA均为反义RNA、短链干扰RNA和小RNA，这些RNA在细胞信使RNA的水平下调节特定的基因表达，作者从超级嗜盐古菌中识别出了一种mRNA干扰酶（MazF-hw mRNA interferase），这种超级嗜盐古菌可以利用一种序列（UUACUCA）来清除RNA，这种序列在视紫红质转录激活剂和古菌的膜蛋白质的信使RNA中量非常多，也就说明了这些蛋白质的表达是通过MazF-hw来调节的，大肠杆菌中必要基因中的这些序列位点被清除以后，大肠杆菌将不再对MazF-hw敏感，研究人员由此便揭示出特定的基因表达可以被序列特异性的mRNA干扰酶所调节，RNA干扰并不仅仅可以通过RNA来进行，而且可以通过蛋白质来调节使基因表达沉默。（生物谷T.Shen编译 Bioon.com）（有问题请及时指正）
doi:10.1038/ncomms1621
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Inhibition of specific gene expressions by protein-mediated mRNA interference
Yoshihiro Yamaguchi,1 Hirofumi Nariya,1, 2 Jung-Ho Park1 & Masayori Inouye1
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.
