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

Many benign mesenchymal tumors are characterized by chromosomal abnormalities of the regions 12q15 or 6p21.3 leading to aberrant expression of either HMGA2 (formerly HMGIC) or HMGA1 (formerly HMGIY). The proteins of both genes belong to the HMGA (formerly HMGI(Y)) family of architectural transcription factors. As a rule, aberrant HMGA transcripts found in a variety of benign tumors have intact coding regions at least for the DNA binding domains with a truncation of their 3′ untranslated regions. Adding this to the finding that an altered HMGA protein level is not always correlated with an increased amount of corresponding mRNA indicates a posttranscriptional expression control mediated by regulatory elements within the 3′UTR. To check if HMGA expression is under control of such elements we performed luciferase assays with several HMGA2 and HMGA1 3′UTRs of different length. Experiments showed that an up to 12-fold increase in luciferase activity is obtained by the truncation of the 3′UTRs suggesting that the expression of HMGA2 and HMGA1 is controlled by negatively acting regulatory elements within their 3′UTR. 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.