BACKGROUND: The nuclear receptor genes
including estrogen receptor β (ERβ)
contain non-conventional internal and terminal exons
and alternative choice of the exons yields multiple mRNA and protein variants with unique structures and functions. However
the genomic structure of the intronic and 3'-downstream regions of the human ERβ gene and the presence of novel ERβ variants with non-conventional sequences have not been re-examined for approximately two decades. Therefore
we attempted to re-characterize the structure of the human ERβ gene and identify novel non-conventional exons and distinct splice variants. METHODS: Rapid amplification of cDNA 3'-end and RT-PCR cloning were performed to isolate human ERβ mRNA variants from the testis. The identified cDNA sequences were mapped on the human genome assembly. Expression profiles of the variants were assessed by RT-PCR analysis. RESULTS: We cloned multiple ERβ mRNA variants with novel nucleotide sequences from the testis and identified several alternative splice sites
3'-elongation of conventional coding exons
and novel terminal exons in the human ERβ gene. The variants encode C-terminally truncated ERβ proteins termed ERβ6
ERβ7
ERβEx. 4L
and ERβEx. 6L. Furthermore
we identified the presence of exon 7-defective forms of ERβ2/βcx
ERβ4
ERβ6
and ERβ7. Subsequently
we determined distinct expression patterns of the variants in human peripheral organs and brain subregions. CONCLUSION: This study elucidated the complicated genomic organization and splicing patterns of the human ERβ gene that contribute to the distinct heterogeneity of human ERβ mRNAs and proteins.
