1. Expression of oestrogen receptor β isoforms is regulated by transcriptional and post-transcriptional mechanisms.
- Author
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Laura Smith, Louise J. Coleman, Michele Cummings, Sampoorna Satheesha, Spencer O. Shaw, Valerie Speirs, and Thomas A. Hughes
- Subjects
ESTROGEN ,GENE expression ,GENETIC transcription ,BREAST tumors ,NON-coding RNA ,MEDICAL literature ,TUMOR growth - Abstract
Although ERs (oestrogen receptors) mediate breast tumour behaviour, the precise role of ERβ remains unclear. This is mainly because analyses have been complicated by the presence in breast tissue of three ERβ protein variants (ERβ1, ERβ2 and ERβ5) that derive from differential 3′ splicing. We have recently identified the first known mechanisms responsible for the differential control of isoform expression, involving regulation of translation via 5′-UTRs (untranslated regions). In the present study, we have uncovered further complexity involving the influence of multiple promoters and cross-talk between 5′- and 3′-UTRs. We demonstrate that full-length ERβ mRNAs are transcribed from three separate promoters; two promoters are well-established within the literature, whereas the third represents a novel finding. Each promoter produces transcripts with distinct 5′-UTRs. The differential 3′ splicing that produces transcripts coding for the ERβ isoforms also defines isoform-specific 3′-UTRs. We identified exact 3′-UTR sequences for each isoform, and have shown that alternative polyadenylation sites are used in a cell-type specific manner to produce transcripts with 3′-UTRs of different lengths. Critically, we show that 5′- and 3′-UTRs combine to specify the efficiencies with which individual transcripts are translated, with 3′-UTR length having a key influence. In addition, we demonstrate how 17β-oestradiol, a key driver of breast cancer development, affects the regulation of ERβ expression at both transcriptional and translational levels. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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