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。在近期的《細(xì)胞》雜志上,，兩個(gè)研究小組的成員發(fā)現(xiàn)了miRNAs與靶mRNA之間的新關(guān)系：他們提出miRNAs將靶基因mRNA的水平調(diào)整到了一種最佳水平，并用不同的實(shí)驗(yàn)進(jìn)行了證明,。
在第一篇文章中,，來自德國(guó)歐洲分子生物實(shí)驗(yàn)室（European Molecular Biology Laboratory，EMBL）和國(guó)力新加坡大學(xué)Temasek生命科學(xué)實(shí)驗(yàn)室的研究人員利用一種果蠅miRNA突變研究分析認(rèn)為miRNAs將靶基因的水平調(diào)整到了最佳水平,，并由于這種小RNA的保守性,，因此提出在人類也存在這種關(guān)聯(lián)。
microRNAs（miRNAs）通過綁定到特異性mRNA靶標(biāo)上來進(jìn)行轉(zhuǎn)錄后基因調(diào)控,，目前雖然對(duì)這兩者之間的關(guān)系已加深了了解,，但是miRNAs與靶標(biāo)之間的調(diào)控關(guān)系依然存在許多未解之謎。
許多miRNAs都能將其靶標(biāo)的表達(dá)減少到不產(chǎn)生影響的水平,，也因此有人提出miRNAs也許是將靶基因的水平調(diào)整到了一種最佳水平,，在第一篇文章中，研究人員分析了將果蠅中保守的miRNA：miR-8突變之后的結(jié)果,，從中他們識(shí)別了atrophin基因是miR-8的直接靶標(biāo)（Atrophin-1是齒狀核紅核蒼白球路易氏體退行性病變（DRPLA）的致病基因）,，miR-8突變表型中atrophin基因活性有所增高，導(dǎo)致大腦中細(xì)胞調(diào)亡水平增高,。
miR-8表達(dá)細(xì)胞中atrophin水平降低到miR-8調(diào)控水平以下是有害的,，這說明兩者之間存在“調(diào)節(jié)靶標(biāo)”的關(guān)系。由于果蠅的atrophin與哺乳動(dòng)物轉(zhuǎn)錄調(diào)控因子atrophin家族相關(guān),，因此研究人員也認(rèn)為這種存在于miR-8和atrophin同源基因之間的相互關(guān)系在哺乳動(dòng)物中是保守,，這也意味著人類也可能存在這種關(guān)聯(lián)。
原始出處：
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
[email protected]
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.
