MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell: Introducing microRNA pharmacogenomics

Abstract

MicroRNAs are evolutionarily conserved small non-coding RNAs known to inhibit the translation of proteins by binding to the target transcript in the 3′ untranslated region. Functional polymorphisms in 3′ UTRs of several genes have been reported to be associated with diseases by affecting gene expression. The mechanism by which these polymorphisms affect gene expression and induce variability in a cell is not well understood. It has been suggested that these polymorphisms may interfere with regulatory elements that bind to untranslated region of a gene. Recently, a novel class of functional polymorphisms termed miRSNPs/polymorphisms was reported.1,2 defined as a polymorphism present at or near a microRNA binding sites of functional genes that can affect gene expression by interfering with a miRNA function. The work elucidated the mechanism of a functional miRSNP 829C→ T present in 3′ UTR of dihydrofolate reductase, an important drug target. The SNP interferes with the miR24 microRNA function and leads to DHFR over expression and methotrexate resistance. In this article we highlight the importance of these miRSNPs or miR-polymorphisms in gene regulation and the mechanism by which these miRSNPs can induce variability in the SNP expressing mutant cell by using drug resistance as an example. ©2008 Landes Bioscience.