The new LAW of microRNA-mediated gene silencing

MicroRNAs （miRNAs）是一类存在于我们身体所有细胞中的小rna，最近被发现可以抑制基因表达。它们的作用机制深远而复杂；每个miRNA可能控制许多基因，据估计，miRNA调节多达1/3的人类基因的表达。人类基因通过mRNA中间体表达为蛋白质，mRNA中间体是所讨论的DNA编码基因的副本。然后，这种mRNA从细胞核进入细胞质，在细胞质中，编码被“翻译”或制成蛋白质，从而表达。MicroRNAs通过两种假设机制之一抑制基因表达：(1)与mRNA配对，在mRNA翻译成蛋白质的早期停止mRNA的表达，起始阻断；(2)与目标mRNA配对，在mRNA翻译成蛋白质的过程中停止mRNA的表达，从而停止蛋白质的产生，起始阻断。在这两种情况下，mRNA都没有被翻译成蛋白质，但（抑制）mRNA保持完整。MicroRNAs在不同的生物体、细胞发育阶段和疾病模式中表现出不同的表达模式，并在调节基因表达中发挥重要作用。尽管近年来我们对miRNA生物学有了大量的了解，但我们仍然不知道细胞如何执行miRNA介导的基因沉默的确切机制，以及它如何决定不同类型的miRNA沉默（启动或启动后阻断）。我的研究小组已经确定了两组不同的蛋白质，(1)称为LIMD1， Ajuba, WTIP （LAW）和(2)称为Zyxin， LPP, TRIP6 （ZLT）。我们认为这可能代表了mirna导向基因沉默的缺失成分。此外，这两组蛋白质可以帮助细胞决定执行哪种类型的miRNA沉默。使用LAW组并使用起始块，或者使用ZLT组并诱导一个后起始块。我们的研究旨在确定这些可能性，从而确定最终将对改善人类和动物健康产生长期影响的新生物学。

MicroRNAs (miRNAs) are a class of small RNAs within all the cells of our body that have recently been found to inhibit gene expression. Their mechanism of action is far reaching and complex; each miRNA may control many genes and it is estimated that miRNAs regulate expression of up to 1/3 of all human genes. Human genes are expressed as proteins via a mRNA intermediate which is a copy of the DNA encoded gene in question. This mRNA then travels from the nucleus to the cytoplasm where the code is 'translated' or made into protein and thus expressed. MicroRNAs operate to inhibit gene expression by one of two hypothesised mechanisms: (1) by pairing with a mRNA- and stopping the mRNA being expressed very early on in its translation into protein, initiation block and (2) pairing with target mRNA - stopping the mRNA being expressed in the middle of its translation into protein therefore halting protein production, post-initiation block. In either case the mRNA is not translated into protein but (repressed) but the mRNA remains intact. MicroRNAs show distinct expression patterns in different organisms, cell development stages, and disease models and play an important role in regulating gene expression. Even though we have learnt a great deal about miRNA biology in recent years we still do not know the precise mechanism(s) of how the cell performs miRNA-mediated gene silencing and furthermore how it decides between the different types of miRNA silencing (initiation or post-initiation block). My research group has identified two distinct groups of proteins, (1) called LIMD1, Ajuba, WTIP (LAW) and (2) called Zyxin, LPP, TRIP6 (ZLT). Which we believe may represent the missing components to enable miRNA-directed gene silencing. Furthermore, these two groups of protein may then help the cell decide which type of miRNA silencing to perform. Employ the LAW group and use initiation block, or the ZLT group and induce a post-initiation block. Our research is aimed at determining these possibilities and therefore new biology which will ultimately impact on improved human and animal health in the long term.