1月3日,，國際著名雜志自然-通訊Nature Communications在線刊登了美國和日本的研究人員的最新研究成果“Inhibition of specific gene expressions by protein-mediated mRNA interference。”,，文章中,，作者報(bào)道了一種新的抑制基因表達(dá)的方法,，作者運(yùn)用蛋白質(zhì)介導(dǎo)的RNA干擾的方法從而來抑制特定基因的表達(dá)。
RNAi(RNA interference)即指的是與靶基因同源的雙鏈RNA誘導(dǎo)的特異轉(zhuǎn)錄后基因沉默表達(dá)的一種現(xiàn)象,，RNAi的作用機(jī)理是核酸內(nèi)切酶Dicer將dsRNA（雙鏈RNA）切割成多個(gè)具有特定長(zhǎng)度和結(jié)構(gòu)的小片段RNA即siRNA,，siRNA在細(xì)胞內(nèi)RNA解旋酶的作用下解鏈成正義鏈和反義鏈，然后反義siRNA再與體內(nèi)一些酶結(jié)合形成RNA誘導(dǎo)的沉默復(fù)合物(RNA-induced silencing complex,，RISC),。RISC與外源性基因表達(dá)的mRNA的同源區(qū)進(jìn)行特異性結(jié)合并且在結(jié)合部位切割mRNA，被切割后的斷裂mRNA隨即降解,。siRNA不僅能引導(dǎo)RISC切割同源單鏈mRNA,，而且可作為引物與靶RNA結(jié)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切割產(chǎn)生大量的次級(jí)siRNA,，從而使RNAi的作用進(jìn)一步放大，最終將靶mRNA完全降解,。如今RNA干擾技術(shù)已經(jīng)發(fā)展成為基因治療,、基因結(jié)構(gòu)功能研究的快速而有效的方法,。
在文章中，研究人員首次報(bào)道了運(yùn)用蛋白質(zhì)介導(dǎo)的RNA干擾的方法,，一把情況下,，RNAi涉及的RNA均為反義RNA、短鏈干擾RNA和小RNA,，這些RNA在細(xì)胞信使RNA的水平下調(diào)節(jié)特定的基因表達(dá),，作者從超級(jí)嗜鹽古菌中識(shí)別出了一種mRNA干擾酶（MazF-hw mRNA interferase），這種超級(jí)嗜鹽古菌可以利用一種序列（UUACUCA）來清除RNA,，這種序列在視紫紅質(zhì)轉(zhuǎn)錄激活劑和古菌的膜蛋白質(zhì)的信使RNA中量非常多，也就說明了這些蛋白質(zhì)的表達(dá)是通過MazF-hw來調(diào)節(jié)的,，大腸桿菌中必要基因中的這些序列位點(diǎn)被清除以后,，大腸桿菌將不再對(duì)MazF-hw敏感，研究人員由此便揭示出特定的基因表達(dá)可以被序列特異性的mRNA干擾酶所調(diào)節(jié),，RNA干擾并不僅僅可以通過RNA來進(jìn)行,，而且可以通過蛋白質(zhì)來調(diào)節(jié)使基因表達(dá)沉默。（生物谷T.Shen編譯 Bioon.com）（有問題請(qǐng)及時(shí)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.
