Production of Three Distinct mRNAs of 150 kDa Oxygen-Regulated Protein (ORP 150) by Alternative Promoters: Preferential Induction of One Species under Stress Conditions

抄録

150 kDa oxygen-regulated protein (ORP 150) is one of the endoplasmic reticulum (ER)-resident stress proteins. We have cloned and sequenced the entire human ORP 150 gene covering over 15-kb. Analyses of transcription initiation sites and transcriptional regulatory sequences revealed that at least three distinct mRNA species were produced by alternative promoters: two of them starting from alternative exon 1 (1 A or 1 B), and the third one starting from exon 2, six nucleotides upstream of the first AUG initiation codon. Among them, the transcript that begins with exon 1 B was preferentially induced by hypoxia or tunicamycin treatment. A cis-acting segment involved in the stress-dependent induction was found at the 5'-end of exon 1 A, which could account for the selective induction of the transcription from exon 1 B. Furthermore, in vitro analyses of translation of the third mRNA suggested the constitutive expression of the cytosolic ORP 150 due to the lack of the signal peptide resulting from differential translation initiation.