IDENTIFICATION OF A FUNCTIONAL-ROLE FOR THE 3' REGION OF THE HUMAN ESTROGEN-RECEPTOR GENE

A well-conserved feature of the steroid receptor gene family is the presence of an exceptionally long 3' untranslated region (UTR). Analysis of this sequence from the human oestrogen receptor (hER) gene showed the presence of a number of AT-rich regions that included thirteen repeats of the ATTTA motif, an element known to have a destabilizing effect in other systems, In the region 3' of the gene there were a further eight copies of this pentamer. Also located in this sequence were two members of the Alu repetitive family in inverse orientation and in a tandem arrangement. Transfection experiments in which the 3' UTR and 3' flanking sequence were included in chloramphenicol acetyltransferase expression vectors revealed a large destabilization effect with several different fragments. This inherent instability appears to be determined by the primary nucleotide sequence but may act in conjunction with other factors. This post-transcriptional regulatory mechanism may contribute to the control of the level of the hER mRNA.