MicroRNA靶基研究.doc

microrna靶基因研究 MicroRNAs (miRNAs)是一种大小约21—23个碱基的单链小分子RNA，是由具有发夹结构的约70-90个碱基大小的单链RNA前体经过dicer酶加工后生成，不同于siRNA（双链）但是和siRNA密切相关。据推测，这些非编码小分子RNA（miRNAs）参与调控基因表达，但其机制区别于siRNA介导的mRNA降解。第一个被确认的miRNA是在线虫中首次发现的lin-4 和let-7，随后多个研究小组在包括人类、果蝇、植物等多种生物物种中鉴别出数百个miRNAs。　　最早被发现的两个miRNAs——lin-4 and let-7被认为是通过不完全互补结合到目标靶mRNA 3’非编码区端，以一种未知方式诱发蛋白质翻译抑制，进而抑制蛋白质合成，阻断mRNA的翻译。多个果蝇miRNAs也被发现和他们的目标靶mRNAs的3’非编码区有部分同源。由于miRNAs和其潜在的目标靶之间并非完全互补，这使得通过信息学的方法鉴定miRNA的目标靶位点变得困难。因而也无法确定miRNAs的作用方式是什么，以何种机制影响mRNA的翻译，以何种方式调控基因表达。miRNAs的作用目标靶和活性机制一直是各地的研究人员的关注热点。 总结了一些microrna靶基因方法的比较重要的文献，与大家共享。 Combinatorial microRNA target predictions Azra Krek1,2,4, Dominic Grün1,4, Matthew N Poy3,4, Rachel Wolf1, Lauren Rosenberg1, Eric J Epstein3, Philip MacMenamin1, Isabelle da Piedade1, Kristin C Gunsalus1, Markus Stoffel3 & Nikolaus Rajewsky1 Abstract MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3′ untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript1, 2, 3. Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals. /ng/journal/v37/n5/ful