The new LAW of microRNA-mediated gene silencing

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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.