The expression of HMGA genes is regulated by their 3 ' UTR

Many benign mesenchymal tumors are characterized by chromosomal abnormaliti es of the regions 12q15 or 6p21.3 leading to aberrant expression of either HMGA2 (formerly HMGIC) or HMGA1 (formerly HMGIY). The proteins of both gene s belong to the HMGA (formerly HMGI(Y)) family of architectural transcripti on factors. As a rule, aberrant HMGA transcripts found in a variety of beni gn tumors have intact coding regions at least for the DNA binding domains w ith a truncation of their 3' untranslated regions. Adding this to the findi ng that an altered HMGA protein level is not always correlated with an incr eased amount of corresponding mRNA indicates a posttranscriptional expressi on control mediated by regulatory elements within the 3'UTR. To check if HM GA expression is under control of such elements we performed luciferase ass ays with several HMGA2 and HMGA1 3'UTRs of different length. Experiments sh owed that an up to 12-fold increase in luciferase activity is obtained by t he truncation of the 3'UTRs suggesting that the expression of HMGA2 and HMG A1 is controlled by negatively acting regulatory elements within their 3'UT R. Chromosomal aberrations affecting the HMGA genes may therefore influence their expression by an altered stability of the truncated transcripts as a result of the cytogenetic aberrations.