INDUCTION OF TRANSLATION BY THE 5'-UNTRANSLATED REGION OF HUMAN ANDROGEN RECEPTOR MESSENGER-RNA

Androgens and androgen receptor (AR) play important roles in sexual di fferentiation and prostatic cancer cell proliferation. To investigate the regulation of AR expression, a 2-kilobase pair 5'-flanking region of human AR gene including a 0.6-kilobase pair 5'-untranslated region (5'-UTR) was ligated to a chloramphenicol acetyltransferase (CAT) gene and characterized by CAT assay after transfection into HeLa cells. Th e results revealed that AR 5'-UTR was absolutely needed for the induct ion of CAT activity, but could not function as an enhancer for the AR transcription. A further study using a 180 base pairs (+21 to +202 inc luding a stem-loop secondary structure at +109 to +129) within the AR 5'-UTR demonstrated that this region was sufficient to induce more CAT activity without changing the CAT mRNA expression. Taken together, th ese results strongly suggested that 5'-UTR of AR mRNA plays an essenti al role in the induction of AR translation, which may represent the fi rst reported translational induction mechanism in the steroid receptor superfamily.