Silencing genes with RNA
Genes are expressed or transcribed to produce a protein. Messenger RNA (mRNA) passes this code from the DNA to the ribosomes for protein assembly. Many molecules including miRNAs can interfere with this process and repress gene translation through mRNA degradation by removal of adenyl groups (deadenylation). Unravelling the underlying mechanisms could help in the development of therapeutic tools that selectively disable the production of proteins involved in disease development. Researchers in the 'In-vitro system for mammalian miRNA function' (MIRNA MECHANISM) project have analysed how miRNAs act by manipulating the biochemistry of the gene transcription system extracted from the fruit fly Drosophila. The scientists showed that if mRNA has a poly(A) tail composed of many adenyl groups joined together in a polymer fashion, the repression is more effective. The poly(A)-binding protein (PABP) mediates the extent of gene silencing. The researchers looked at the whole miRNA-mediated silencing complex (miRISC) and mapped the proteins responsible. They found that PABP actually acts as a co-repressor of gene translation and that the longer the poly (A) tail, the stronger the inhibition. This finding overturns current models that propose that miRISC interferes with a positive function in PABP in translation. The results of the MIRNA MECHANISM project have wide-ranging significance for disease control and human health. miRNAs are implicated in diseases such as cancer and diabetes. Information on the action and structure of these molecular players is vital for the development of designer drugs to silence the genes behind chronic ill-health.
Keywords
Repression, miRNA, mRNA, adenyl, poly(A) tail, poly(A)-binding protein, gene silencing, miRSC
