Induction of translation by the 5'-untranslated region of human androgen receptor mRNA.

Abstract

Androgens and androgen receptor (AR) play important roles in sexual differentiation 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. The results revealed that AR 5'-UTR was absolutely needed for the induction 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 including 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, these results strongly suggested that 5'-UTR of AR mRNA plays an essential role in the induction of AR translation, which may represent the first reported translational induction mechanism in the steroid receptor superfamily.