生物谷綜合：微小RNA (microRNA,，簡(jiǎn)稱miRNA)是生物體內(nèi)源長(zhǎng)度約為20－23個(gè)核苷酸的非編碼小RNA，通過與靶mRNA的互補(bǔ)配對(duì)而在轉(zhuǎn)錄后水平上對(duì)基因的表達(dá)進(jìn)行負(fù)調(diào)控,，導(dǎo)致mRNA的降解或翻譯抑制,。到目前為止，已報(bào)道有幾千種miRNA存在于動(dòng)物,、植物,、真菌等多細(xì)胞真核生物中，進(jìn)化上高度保守,。
一般而言,，編碼miRNAs的基因最初產(chǎn)生一個(gè)長(zhǎng)的pri-RNA分子,，這種初期分子還必須被剪切成約70-90個(gè)堿基大小、具發(fā)夾結(jié)構(gòu)單鏈RNA前體（pre-miRNA）并經(jīng)過Dicer酶加工后生成,。然而近期發(fā)表在Genes & Development（1月1日）的三篇獨(dú)立文章在果蠅中發(fā)現(xiàn)了一種雙向性轉(zhuǎn)錄（bidirectionally transcribed）microRNA,，這也許提示了一種新機(jī)制，對(duì)于了解miRNA功能的多樣性來說意義重大,。
在頭兩篇文章中,，來自紐約約斯隆/凱德琳癌癥研究中心（Memorial Sloan-Kettering Cancer Center）發(fā)育生物學(xué)系的賴教授（Eric C. Lai，2007年獲得NHGRI果蠅及線蟲研究項(xiàng)目190萬美元資助,，生物谷注）領(lǐng)導(dǎo)的研究團(tuán)隊(duì)和麻省理工學(xué)院的Manolis Kellis領(lǐng)導(dǎo)的研究小組分別發(fā)現(xiàn)Hox miRNA位點(diǎn)的反義轉(zhuǎn)錄（antisense transcription）：miR-iab-4能產(chǎn)生一種新的miRNA前體——mir-iab-8,，繼而成為有調(diào)控活性的RNAs。
反義轉(zhuǎn)錄,，其產(chǎn)物就是與正義的RNA互補(bǔ)的反義RNA(或者稱反義轉(zhuǎn)錄本),，反義RNA可以通過與正義RNA的互補(bǔ)結(jié)合實(shí)現(xiàn)轉(zhuǎn)錄后基因沉默，從而控制基因表達(dá),。在這里發(fā)現(xiàn)的反義轉(zhuǎn)錄產(chǎn)物mir-iab-8在異位表達(dá)（ectopical expressed,，生物谷注）的時(shí)候，可以通過直接抑制Hox基因靶標(biāo)產(chǎn)生同源異性表型（homeotic phenotype,，生物谷注）。
而在第三篇文章中,，來自哈佛醫(yī)學(xué)院的Welcome Bender博士則證明了miR-iab-4的敲除揭示了一種從相反鏈轉(zhuǎn)錄的miRNA的存在,，而且反義miRNA的缺失會(huì)引起一個(gè)hox基因的些輕微去抑制（derepression）。
這些在果蠅和哺乳動(dòng)物中發(fā)現(xiàn)的額外的反義miRNA說明這種新機(jī)制也許能增加科學(xué)家們對(duì)miRNA功能的多樣化的了解,。
在07年11月份的《Cell》上,，來自瑞士日內(nèi)瓦大學(xué)細(xì)胞生物學(xué)系的研究人員也發(fā)現(xiàn)了一種不依賴于RNAi（RNA干擾）的基因沉默機(jī)制：他們?cè)卺劸平湍钢邪l(fā)現(xiàn)反義RNA穩(wěn)定（Antisense RNA Stabilization）能通過組蛋白去乙酰化引起轉(zhuǎn)錄基因沉默,。這些研究都進(jìn)一步揭示了生物體中基因沉默的多樣化,。
生物谷推薦英文原文：
原文一：
GENES & DEVELOPMENT 22:26-36, 2008
Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci
David M. Tyler1, Katsutomo Okamura1, Wei-Jen Chung1, Joshua W. Hagen1, Eugene Berezikov2, Gregory J. Hannon3, and Eric C. Lai1,4
1 Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10021, USA; 2 Hubrecht Institute, Utrecht 3584 CT, The Netherlands; 3 Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
Many microRNA (miRNA) loci exhibit compelling hairpin structures on both sense and antisense strands; however, the possibility that a miRNA gene might produce functional species from its antisense strand has not been examined. We report here that antisense transcription of the Hox miRNA locus mir-iab-4 generates the novel pre-miRNA hairpin mir-iab-8, which is then processed into endogenous mature miRNAs. Sense and antisense iab-4/iab-8 miRNAs are functionally distinguished by their distinct domains of expression and targeting capabilities. We find that miR-iab-8-5p, like miR-iab-4-5p, is also relevant to Hox gene regulation. Ectopic mir-iab-8 can strongly repress the Hox genes Ultrabithorax and abdominal-A via extensive arrays of conserved target sites, and can induce a dramatic homeotic transformation of halteres into wings. We generalize the antisense miRNA principle by showing that several other loci in both invertebrates and vertebrates are endogenously processed on their antisense strands into mature miRNAs with distinct seeds. These findings demonstrate that antisense transcription and processing contributes to the functional diversification of miRNA genes.
[Keywords: BX-C; antisense; homeotic gene; microRNA]]
Received September 13, 2007; revised version accepted November 6, 2007.
4 Corresponding author.
E-MAIL [email protected] ; FAX (212) 717-5604.
