THREE DISTINCT PROMOTERS DIRECT TRANSCRIPTION OF DIFFERENT 5′ UNTRANSLATED REGIONS OF THE HUMAN INTERLEUKIN 1 TYPE I RECEPTOR: A POSSIBLE MECHANISM FOR CONTROL OF TRANSLATION

Abstract

The 5′ untranslated regions (UTR) of the human interleukin 1 (IL-1) type I receptor (IL—1RI) are encoded by one common exon (exon 2) but one of three distinct exons 1 (termed exon 1A, 1B, and 1C). These exons span approximately 50 Kb of genomic DNA. Exons 1A and 1B have multiple transcriptional initiation sites, whereas the promoter for exon 1C uses a single start site. There are no ‘TATA’ or ‘CAAT’ boxes, indicating that these promoters belong to the family of housekeeping gene promoters. Computer sequence analysis of exons 1A, 1B, and 1C predicts the potential to form stable secondary structures (ΔG° 1A= −72.2 Kcal/mol, ΔG° 1B= −125.8 Kcal/mol, ΔG° 1C= −255.4 Kcal/mol). Exon 1C appears to be the most stable whereas exon 1A would yield a mRNA species more likely to be translated than those derived from exon 1B or 1C. The 5′ UTR of exon 1C is also rich (75%) in GC which might inhibit expression. Therefore, we studied the effect of exon 1C on chloramphenicol acetyltransferase (CAT) activity. Deletion of 183 or 296 base pairs from this GC rich region was shown to increase CAT activity. In addition, insertion of a GC-rich fragment of exon 1C inhibited CAT activity driven by SV40 promoter. These results suggest that the 5′ UTR exon 1C of the human IL—1RI may exert a suppressive effect on the translation of IL-1RI transcripts.