The 3′-Untranslated Region of the Human Estrogen Receptor α Gene Mediates Rapid Messenger Ribonucleic Acid Turnover1

Human estrogen receptor-α messenger RNA (hERα mRNA) has a relatively short half-life, which was determined to be approximately 5 h in MCF-7 cell line after actinomycin D treatment. The 3′-untranslated region (3′UTR) of hERα mRNA was previously shown to completely down-regulate chloramphenicol acetyltransferase activity when present at the 3′-end of chloramphenicol acetyltransferase transcripts, suggesting a destabilizing function of the hERα 3′UTR sequence. Chimeric genes composed of a serum-inducible Fos promoter, GH-coding sequences, and different segments of the hERα complementary DNA 3′UTR sequence were used to confirm this hypothesis and to localize the RNA region responsible for the destabilizing effect. The presence of the complete hERα 3′UTR reduced the half-life of the reporter mRNA from more than 24 to 3 h. When the hERα 3′UTR was subdivided into four fragments (UTR1–4), one fragment, UTR2, retained the most ability to down-regulate the reporter mRNA (t1/2 = 4 h). A stretch of four AUUUA motifs ...