MicroRNAs - Future drug targets.?
MicroRNAs - Future drug targets.?
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DOI：
10.1002/anie.200601537
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Arenz, Christoph
中科院分区：
文献类型：
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作者：
Arenz, Christoph
越来越多的证据表明，真核生物的基因调控在很大程度上是在RNA水平上进行的。[1]生物学家和内科医生正在对一组内源性调控RNA分子，即所谓的microRNAs(MiRNAs)进行深入的研究。这些小的RNA分子不仅被认为参与了近30%的人类基因的调控[2]，而且越来越多的数据点指向miRNA表达模式的特定变化与各种疾病之间的联系。microRNA是由所谓的初级microRNA在细胞核中形成的(pri-miRNAs，图1)。这些转录本可以在特定启动子的控制下自动产生，也可以通过RNA聚合酶II从编码蛋白质的初级转录本的内含子中产生。一个或多个前体miRNAs(前miRNAs)然后通过核糖核酸酶DROSHA裂解原始RNAs而形成。这些前miRNAs由70-80个核苷酸组成，呈现典型的发夹构象。蛋白Exportin 5将前miRNAs从细胞核运输到胞浆中。在胞浆中，核糖核酸酶Dester随后对螺旋茎的两条链进行核裂解。由此得到的miRNA是
A growing body of evidence suggests that gene regulation in eukaryotes takes place to a large extent on the RNA level.[1] A group of endogenous regulatory RNA molecules, the so-called microRNAs (miRNAs), are being intensively examined by biologists and physicians. These small RNA molecules are not only believed to be involved in the regulation of nearly 30% of all human genes [2] but an ever-increasing amount of data points towards a connection between specific changes in miRNA expression patterns and various diseases.MicroRNAs are formed in the cell nucleus from so-called primary micro-RNAs (pri-miRNAs, Figure1). These transcripts can be produced either autonomously under the control of a specific promoter or from the intron of a protein-encoding primary transcript through RNA polymeraseII. One or more precursor miRNAs (pre-miRNAs) are then formed by cleavage of the primiRNAs by the ribonuclease Drosha. These pre-miRNAs are made up of 70–80 nucleotides and exhibit a typical hairpin conformation. The pre-miRNAs are transported out of the nucleus into the cytosol by the protein exportin 5. In the cytosol, the ribonuclease Dicer then nucleolytically cleaves both strands of the helical stem. The resulting miRNA is