生物谷綜合：微小RNA (microRNA,，簡稱miRNA)是生物體內源長度約為20－23個核苷酸的非編碼小RNA，通過與靶mRNA的互補配對而在轉錄后水平上對基因的表達進行負調控,，導致mRNA的降解或翻譯抑制。到目前為止,，已報道有幾千種miRNA存在于動物,、植物、真菌等多細胞真核生物中,，進化上高度保守,。
一般而言，編碼miRNAs的基因最初產生一個長的pri-RNA分子,，這種初期分子還必須被剪切成約70-90個堿基大小,、具發(fā)夾結構單鏈RNA前體（pre-miRNA）并經過Dicer酶加工后生成。然而近期發(fā)表在Genes & Development（1月1日）的三篇獨立文章在果蠅中發(fā)現(xiàn)了一種雙向性轉錄（bidirectionally transcribed）microRNA,，這也許提示了一種新機制,，對于了解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)育生物學系的賴教授（Eric C. Lai,，2007年獲得NHGRI果蠅及線蟲研究項目190萬美元資助，生物谷注）領導的研究團隊和麻省理工學院的Manolis Kellis領導的研究小組分別發(fā)現(xiàn)Hox miRNA位點的反義轉錄（antisense transcription）：miR-iab-4能產生一種新的miRNA前體——mir-iab-8,，繼而成為有調控活性的RNAs,。
反義轉錄，其產物就是與正義的RNA互補的反義RNA(或者稱反義轉錄本),，反義RNA可以通過與正義RNA的互補結合實現(xiàn)轉錄后基因沉默,，從而控制基因表達。在這里發(fā)現(xiàn)的反義轉錄產物mir-iab-8在異位表達（ectopical expressed,，生物谷注）的時候,，可以通過直接抑制Hox基因靶標產生同源異性表型（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錄的miRNA的存在,，而且反義miRNA的缺失會引起一個hox基因的些輕微去抑制（derepression）。
這些在果蠅和哺乳動物中發(fā)現(xiàn)的額外的反義miRNA說明這種新機制也許能增加科學家們對miRNA功能的多樣化的了解,。
在07年11月份的《Cell》上,，來自瑞士日內瓦大學細胞生物學系的研究人員也發(fā)現(xiàn)了一種不依賴于RNAi（RNA干擾）的基因沉默機制：他們在釀酒酵母中發(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錄基因沉默,。這些研究都進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.
