Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N.
Widespread changes in protein synthesis induced by microRNAs.
Nature. 2008 Sep 4;455(7209):58-63.
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Selbach et al. and Baek et al. present two nice papers that make an important methodological step forward, as both look directly to protein expression as it is modulated by miRNA. They both confirm that miRNA regulates large amounts of proteins, likely directly by binding to seeds in the 3’ ends of their target mRNA, but apparently also in a more indirect way by the regulation of the expression of some master regulators (e.g., Dicer in the Selbach paper). The big challenge is now to dissect the functional significance of this type of regulation and how the hundreds of microRNAs act together to regulate the overall expression pattern of proteins in cells and tissues in real life. There were already some hints in the past showing that specific microRNAs can reprogram cells in, for instance, a neuronal phenotype.
In vivo studies in the intact animals are now needed to correlate loss or gain of specific microRNAs to specific phenotypes, and those studies should be combined with a systematic analysis to see how the proteins affected by the microRNA are involved (or not) in the establishment of these phenotypes.
Concerning the medical use of microRNA: we are far away from any practical application (apart maybe from diagnostics). It is clear that we need to study this highly interesting novel dimension to the regulation of protein expression in much deeper detail. However, the relevance of the microRNA system for complex diseases can be easily extrapolated: dysregulation of this system could be involved in neurodegenerative disorders or psychiatric disorders, where multiple small problems ultimately could cause global brain failure.
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