-
生物通官微
陪你抓住生命科技
跳动的脉搏
华裔学者等三篇文章发表miRNA重要发现
【字体: 大 中 小 】 时间:2008年01月03日 来源:生物通
编辑推荐:
近期发表在《Genes & Development》(1月1日)的三篇独立文章在果蝇中发现了一种双向性转录(bidirectionally transcribed)microRNA,这也许提示了一种新机制,对于了解miRNA功能的多样性来说意义重大。
一般而言,编码miRNAs的基因最初产生一个长的pri-RNA分子,这种初期分子还必须被剪切成约70-90个碱基大小、具发夹结构单链RNA前体(pre-miRNA)并经过Dicer酶加工后生成。然而近期发表在《Genes & Development》(1月1日)的三篇独立文章在果蝇中发现了一种双向性转录(bidirectionally transcribed)microRNA,这也许提示了一种新机制,对于了解miRNA功能的多样性来说意义重大。
在头两篇文章中,来自纽约约斯隆/凯德琳癌症研究中心(Memorial Sloan-Kettering Cancer Center)发育生物学系的赖教授(Eric C. Lai,2007年获得NHGRI果蝇及线虫研究项目190万美元资助,生物通注)领导的研究团队和麻省理工学院的Manolis Kellis领导的研究小组分别发现Hox miRNA位点的反义转录(antisense transcription):miR-iab-4能产生一种新的miRNA前体——mir-iab-8,继而成为有调控活性的RNAs。
反义转录,其产物就是与正义的RNA互补的反义RNA(或者称反义转录本),反义RNA可以通过与正义RNA的互补结合实现转录后基因沉默,从而控制基因表达。在这里发现的反义转录产物mir-iab-8在异位表达(ectopical expressed,生物通注)的时候,可以通过直接抑制Hox基因靶标产生同源异性表型(homeotic phenotype,生物通注)。
而在第三篇文章中,来自哈佛医学院的Welcome Bender博士则证明了miR-iab-4的敲除揭示了一种从相反链转录的miRNA的存在,而且反义miRNA的缺失会引起一个hox基因的些轻微去抑制(derepression)。
这些在果蝇和哺乳动物中发现的额外的反义miRNA说明这种新机制也许能增加科学家们对miRNA功能的多样化的了解。
在07年11月份的《Cell》上,来自瑞士日内瓦大学细胞生物学系的研究人员也发现了一种不依赖于RNAi(RNA干扰)的基因沉默机制:他们在酿酒酵母中发现反义RNA稳定(Antisense RNA Stabilization)能通过组蛋白去乙酰化引起转录基因沉默。这些研究都进一步揭示了生物体中基因沉默的多样化。
(生物通:张迪)
原文摘要:
David M. Tyler, Katsutomo Okamura, Wei-Jen Chung, Joshua W. Hagen, Eugene Berezikov, Gregory J. Hannon, and Eric C. Lai
Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci
『Abstract』
Alexander Stark, Natascha Bushati, Calvin Jan, Pouya Kheradpour, Emily Hodges, Julius Brennecke, David P. Bartel, Stephen M. Cohen, and Manolis Kellis
A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands
『Abstract』
Welcome Bender
MicroRNAs in the Drosophila bithorax complex
『Abstract』
附:
Eric C. Lai
Education
1999 Ph.D. in Biology, University of California at San Diego
1993 B.A., magna cum laude in Biochemistry, Harvard University
Research and Professional Experience
2005 Assistant Member, Department of Developmental Biology
Memorial Sloan-Kettering Cancer Center, New York, NY
2005 Assistant Professor, Program in Cell Biology and Genetics
Weill Cornell Medical School, New York, NY
1999-2005 Postdoctoral fellow, HHMI/Department of Molecular and Cell Biology
University of California at Berkeley, Berkeley, CA
1. "Regulation of the Notch pathway by ubiquitin ligases"
2. "Genomewide analysis of Drosophila microRNA function"
Dr. Gerald M. Rubin, postdoctoral advisor
1993-1999 Predoctoral fellow, Department of Biology
University of California at San Diego, La Jolla, CA
"Pattern formation during Drosophila sensory organ development"
Dr. James W. Posakony, graduate thesis advisor
1992-1993 Undergraduate thesis research, Department of Molecular Biology
Massachusetts General Hospital/Harvard Medical School, Boston, MA
"Spatial expression of ceh-20, a C. elegans PBX-class homeobox gene"
Dr. Gary Ruvkun, undergraduate thesis advisor
Selected Awards and Fellowships:
2005 Career Award in the Biomedical Sciences, Burroughs Wellcome Fund
2004-2006 Special Fellow of the Leukemia and Lymphoma Society
2000-2003 Fellow of the Damon Runyon Cancer Research Foundation
2000 Jane Coffin Childs Memorial Fund for Medical Research Fellowship (declined)
2000 Larry Sandler Memorial Award for Drosophila Research, Finalist
1993-1999 Fellow of the Lucille P. Markey Charitable Trust
1993 Phi Beta Kappa, Harvard College
1991 John Harvard Scholarship
1989 National Merit Scholarship