Then they chose one potentially affected gene at random to explore the ramifications of microRNA editing in depth. As it turned out, the gene they selected, known as PRPS1, codes for an essential enzyme involved in synthesizing uric acid. If levels of the enzyme are poorly regulated, a number of health problems can arise. For example, too-high levels of the enzyme can cause uric acid levels to rise in the blood, triggering painful episodes of gout. Similarly, in the brain, excess uric acid can damage sensory neurons and cause deafness.
Working with a strain of transgenic mice unable to perform RNA editing and normal control mice, the researchers found that a complete lack of the edited version of the microRNA in question had the effect of driving production of the PRPS1 enzyme to about double its normal levels. This, in turn, drove levels of uric acid up to about two times what they should be.
"This confirmed that our original computer prediction of differential targeting by unedited and edited microRNAs of different sets of genes is likely to be correct," Nishikura says. "And in at least the case of the one gene we investigated, this differential has physiological consequences seen in the elevated uric acid levels."
Given the fact that the PRPS1 gene was randomly selected for investigation by the researchers, the findings suggest that a number of other as-yet unidentified disorders may also have their roots in this newly identified microRNA editing process.
Source:The Wistar Institute