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L.M. Partyka, R. Donnelly, P. Frederikse; Expression of Brain Specific miRNAs in Human Lens: Shared Mechanisms of Global Gene Regulation in Lens and Brain . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3136.
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In our earlier studies we initiated investigations into the striking similarities that exist between lens and neuronal cell biology, gene regulation, and development, with a goal of understanding shared mechanisms in lens and brain that contribute to coordinate age–related degenerative disease in both organs. Recently, experiments in our lab demonstrated such parallels extend to lens expression of brain–specific small RNAs termed micro RNAs or miRNAs. Mechanisms of post–transcriptional regulation by miRNAs and small silencing RNAs (siRNAs) overlap, and miRNAs are now known to down–regulate expression of large groups of genes (∼200 each) and define tissue specific expression (Lim et al. Nature, 2005;433:769). miRNAs are conserved across diverse animal species, and have fundamental roles in governing tissue specific expression and development.
Northern blots were used to demonstrate expression of specific small RNAs in lens fibers and brain tissue in rodents and human embryonic lenses. Specific probes for miR–124, miR125b, let–7a and miR–7 were used to determine expression of brain–specific miRNAs in lens. Gene microarrays were used to analyze expression of genes down–regulated by brain–specific miRNAs, in lens.
Our data demonstrate lens expression of brain specific in human fetal lenses and post–natal mouse and rat lenses. Array results thus far indicate that a set of approximately 175 genes down–regulated specifically in brain by miR–124 (Lim et al. 2005) are also coordinately down–regulated in lens.
Fundamental mechanisms of gene regulation involving miRNA post–transcriptional regulation are shared by lens and brain. miRNAs specifically involved in the development of the nervous system are expressed in the lens, along with the down–regulation of a similar set of genes in lens, as in brain. These findings indicate that in addition to expression of neuron specific genes in lens cells we showed in previous studies, fundamental mechanisms of gene regulation involving miRNAs also have a shared role in lens and brain.
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