《Cell》：青年科学家发现miRNA新途径

　　生物通报道：来自美国纽约约斯隆/凯德琳癌症研究中心（Memorial Sloan-Kettering Cancer Center）发育生物学系的研究人员发现了一种不同于正常miRNAs合成途径的新途径，这为进一步解释生物RNA沉默机制提供了重要资料以及新的思路。这一研究成果公布在《Cell》杂志上。

原文摘要：
Cell, Vol 130, 89-100, 13 July 2007
The Mirtron Pathway Generates microRNA-Class Regulatory RNAs in Drosophila
[Abstract]

RNA沉默是存在于生物中的一种古老现象, 是生物抵抗异常DNA(病毒、转座因子和某些高重复的基因组序列)的保护机制, 同时在生物发育过程中扮演着基因表达调控的角色，它可以通过降解RNA、抑制翻译或修饰染色体等方式发挥作用。

RNA沉默存在两种既有联系又有区别的途径: siRNA(small interference RNA)途径和miRNA(microRNA)途径。siRNA途径是由dsRNA(double-stranded RNA)引发的, dsRNA被一种RNaseⅢ家族的内切核酸酶(RNA- induced silencing complex, Dicer)切割成21~26 nt长的siRNA, 通过siRNA指导形成RISC蛋白复合物(RNA-induced silencing complex)降解与siRNA序列互补的mRNA而引发RNA沉默。而miRNA途径中miRNA是含量丰富的不编码小RNA(21~24个核苷酸), 由Dicer酶切割内源性表达的短发夹结构RNA(hairpin RNA, hpRNA)形成。miRNA同样可以与蛋白因子形成RISC蛋白复合物, 可以结合并切割特异的mRNA而引发RNA沉默。尽管引发沉默的来源不同, 但siRNA 和miRNA 都参与构成结构相似的RISC, 在作用方式上二者有很大的相似性。 

在这篇文章中，研究人员描绘了果蝇的一种由短小的内含子发夹结构形成的miRNAs，并将其命名为“mirtrons”。这些miRNAs的关键生物生成过程好像避开了Drosha的剪切，而这对于miRNA生物合成是必需的。

那么mirtrons是如何形成的呢？研究人员发现mirtrons的剪切机制是通过lariat-debranching酶产生miRNA类前体发夹。并且在Exportin-5发夹端口处融入到了正常的miRNA途径过程中，这两种发夹可以被之后的途径中的Dicer-1/loqs处理。这样得到的小RNAs可以很好的匹配靶标，而且研究人员证明这些miRNAs至少能部分的行使功能——通过RNA诱导的沉默复合效应子Ago1。

这些研究成果意义重大，揭示了mirtrons可能是另外一种miRNA型调控性RNAs，这为进一步解释生物RNA沉默机制提供了重要资料以及新的思路。
（生物通：张迪）

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