微小RNA(microRNA，简称miRNA)是生物体内源长度约为20－23个核苷酸的非编码小RNA，通过与靶mRNA的互补配对而在转录后水平上对基因的表达进行负调控，导致mRNA的降解或翻译抑制。在近期的《细胞》杂志上，两个研究小组的成员发现了miRNAs与靶mRNA之间的新关系：他们提出miRNAs将靶基因mRNA的水平调整到了一种最佳水平，并用不同的实验进行了证明。
在第一篇文章中，来自德国欧洲分子生物实验室（European Molecular Biology Laboratory，EMBL）和国力新加坡大学Temasek生命科学实验室的研究人员利用一种果蝇miRNA突变研究分析认为miRNAs将靶基因的水平调整到了最佳水平，并由于这种小RNA的保守性，因此提出在人类也存在这种关联。
microRNAs（miRNAs）通过绑定到特异性mRNA靶标上来进行转录后基因调控，目前虽然对这两者之间的关系已加深了了解，但是miRNAs与靶标之间的调控关系依然存在许多未解之谜。
许多miRNAs都能将其靶标的表达减少到不产生影响的水平，也因此有人提出miRNAs也许是将靶基因的水平调整到了一种最佳水平，在第一篇文章中，研究人员分析了将果蝇中保守的miRNA：miR-8突变之后的结果，从中他们识别了atrophin基因是miR-8的直接靶标（Atrophin-1是齿状核红核苍白球路易氏体退行性病变（DRPLA）的致病基因），miR-8突变表型中atrophin基因活性有所增高，导致大脑中细胞调亡水平增高。
miR-8表达细胞中atrophin水平降低到miR-8调控水平以下是有害的，这说明两者之间存在“调节靶标”的关系。由于果蝇的atrophin与哺乳动物转录调控因子atrophin家族相关，因此研究人员也认为这种存在于miR-8和atrophin同源基因之间的相互关系在哺乳动物中是保守，这也意味着人类也可能存在这种关联。
原始出处：
Cell, Vol 131, 136-145, 05 October 2007
Article
The Conserved microRNA MiR-8 Tunes Atrophin Levels to Prevent Neurodegeneration in Drosophila
Janina S. Karres,1 Valérie Hilgers,1 Ines Carrera,3 Jessica Treisman,3 and Stephen M. Cohen1,2,
1 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
2 Temasek Life Sciences Laboratory, and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604
3 Skirball Institute, New York University, 540 First Avenue, New York, NY 10016, USA
Corresponding author
Stephen M. Cohen
cohen@tll.org.sg
microRNAs (miRNAs) bind to specific messenger RNA targets to posttranscriptionally modulate their expression. Understanding the regulatory relationships between miRNAs and targets remains a major challenge. Many miRNAs reduce expression of their targets to inconsequential levels. It has also been proposed that miRNAs might adjust target expression to an optimal level. Here we analyze the consequences of mutating the conserved miRNA miR-8 in Drosophila. We identify atrophin as a direct target of miR-8. miR-8 mutant phenotypes are attributable to elevated atrophin activity, resulting in elevated apoptosis in the brain and in behavioral defects. Reduction of atrophin levels in miR-8-expressing cells to below the level generated by miR-8 regulation is detrimental, providing evidence for a “tuning target” relationship between them. Drosophila atrophin is related to the atrophin family of mammalian transcriptional regulators, implicated in the neurodegenerative disorder DRPLA. The regulatory relationship between miR-8 and atrophin orthologs is conserved in mammals.
