Complex organization of the 5'-untranslated region of the mouse estrogen receptor α gene: identification of numerous mRNA transcripts with distinct 5'-ends.

The 5'-untranslated region (5'-UTR) of the estrogen receptor α (ERα) gene plays an important role in determining its tissue-specific expression. We examined the 5'-UTRs of the mouse ERα mRNA variants in depth using the Basic Local Alignment Search Tool (BLAST), rapid amplification of 5'-cDNA ends (5'-RACE) and RT-PCR. We demonstrated the presence of multiple variants containing unique 5'-UTRs. We mapped the cDNA sequences onto the mouse genome, and found that both alternative splicing from four different leader exons (A, C, F1, and H) to exon 1, and combinations of 12 internal exons (X1, X2, X3, X4, F2/X5, X6, X7, X8, X9, X10, X11, and B) generate multiple ERα transcripts. Mouse exon B, that has homologies with human exon B and rat exon 0T, was used as an internal exon, not as a leader exon. RT-PCR analysis revealed distinct expression patterns of the variants, suggesting that the alternative promoter usage and alternative splicing are regulated in a tissue-specific manner. Our results indicate that the genomic organization of the mouse ERα gene is complicated as previously shown in the rat ERα gene. In addition, both alternative promoter usage and alternative splicing contribute to the remarkable mRNA diversity of the mouse ERα gene.