非编码RNA学术报告-陈润生院士(PPT).ppt

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * And they hypothesized a regulatory relationship between microRNAs. If this model is true, it will further greatly stimulate the communitys interest in the regulatory role of microRNA, and represents a milestone in exploring microRNAs functionality. 三、NcRNA调节的多样性 miRNA-induced transcriptional inhibition Wang Y, ………………, Patel DJ. Nature. 2008, 456:209-213； Nature. 2008, 456:921-926； Nature.2009, 461:754-761； Nat Struct Mol Biol. 2010, 17：781-787. miRNA-induced transcriptional gene silencingPromotor asscoiated RNA miR-10a inhibits hoxd4 transcription Transfection studies Hoxd4 expression is inhibited by miR-10a Anti-miR-10a increases hoxd4 expression Inhibition not mediated by the 3’UTR Nuclear run-on assay confirms transcriptional inhibition Transcriptional activity in the promoter region of a target gene is required for siRNA-induced transcriptional silencing PNAS 2007 miRNA不仅具有负调控作用，也可以激活基因的表达。Vasudevan 实验室发现, 在细胞周期过程中, miRNA效应在抑制作用和活化作用间摆动. 在静态细胞中(G0期), miRNA活化翻译和上调基因表达, 而在其他细胞循环/增殖期则继续发挥抑制作用. miRNA激活作用与富含腺嘌呤/尿嘧啶元件(adenylate/uridylate-rich?elements, AREs)相关. ARE是miRNA活化翻译的信号, 在miRNA指导下, miRISC复合物成员如Ago, FXRP被招募到ARE上, 激活翻译、上调基因表达. ARE元件是一种mRNA不稳定元件, 位于mRNA 3′UTR，对很多mRNA来说，它都是保守的。 Vasudevan S, Tong Y, Steitz J A. Switching from repression to activation: microRNAs can up-regulate translation. Science, 2007, 318(5858): 1931—1934. 其中一个相互作用的过程并不依赖MicroRNA的seed sequence，并且会激发CEBPA mRNA的释放。这些结果表明，microRNA具有控制细胞命运的双重路径和功效，它不仅通过mRNA来发挥作用，还通过调节蛋白来发挥作用。 Cell, Volume 140, 652-665, 5 March 2010 四、NcRNA是与疾病紧密相关的 Examples of lncRNAs correlated with diseases/disorders（ Kannanganattu V. Prasanth and David L. Spector， Genes Dev. 2007 21: 11-42） ————————————————————————————————————————————————————————————————— NcRNAs