Differentially expressed messenger RNA isoforms of the human estrogen receptor-alpha gene are generated by alternative splicing and promoter usage.
The isolation and characterization of several new human estrogen receptor-alpha (hERalpha) mRNAs are described. Together with those previously identified, they give rise to a total of six hERalpha mRNA isoforms (A-F hERalpha mRNAs). Produced from a single hERalpha gene by multiple promoter usage, all these transcripts encode a common protein but differ in their 5'-untranslated region as a consequence of alternative splicing of five upstream exons (1B-1F). RT-PCR and S1 nuclease mapping analysis of these different hERalpha mRNA isoforms revealed a differential pattern of expression of the hERalpha gene in human tissues and cell types. The A hERalpha mRNA is the main isoform detected in mammary glands or in the tumor cell lines derived from this tissue. In endometrium, the predominant forms are the A and C hERalpha mRNA isoforms, whereas the C and F hERalpha mRNA isoforms are the major forms detected in ovary. Finally, high levels of the E hERalpha mRNA isoform are restricted to the liver with an increased expression in females. Taken together, our results demonstrate that the hERalpha gene is a complex genomic unit exhibiting alternative splicing and promoter usage in a tissue-specific manner.
Flouriot
G
G
European Molecular Biology Laboratory, Heidelberg, Germany.
Griffin
C
C
Kenealy
M
M
Sonntag-Buck
V
V
Gannon
F
F
D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry; D002460:Cell Line; D004717:Endometrium / Q000737:chemistry; D047628:Estrogen Receptor alpha; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010053:Ovary / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis*; D011960:Receptors, Estrogen / Q000235:genetics*; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen