Identification of transcripts initiated from an internal promoter in the c-erbA alpha locus that encode inhibitors of retinoic acid receptor-alpha and triiodothyronine receptor activities

The thyroid hormone receptor-coding locus, cerbA alpha, generates several mRNAs originating from a single primary transcript that undergoes alternative splicing. We have identified for the first time two new transcripts, called TR Delta alpha 1 and TR Delta alpha 2 [mRNA for isoform alpha 1 and alpha 2 of the T-3 receptor (TR), respectively], whose transcription is initiated from an internal promoter located within intron 7 of the c-erbA alpha gene. These two new transcripts exhibit tissue-specific patterns of expression in the mouse. These two patterns are in sharp contrast with the expression patterns of the full-length transcripts generated from the c-erbA alpha locus. TR Delta alpha 1 and TR Delta alpha 2 mRNAs encode N-terminally truncated isoforms of T3R alpha 1 and T3R alpha 2, respectively. The protein product of TR Delta alpha 1 antagonizes the transcriptional activation elicited by T-3 and retinoic acid. This protein inhibits the ligand-induced activating functions of T3R alpha 1 and g-cis-retinoic acid receptor-alpha but does not affect the retinoic acid-dependent activating function of retinoic acid receptor-alpha. We predict that these truncated proteins may work as down-regulators of transcriptional activity of nuclear hormone receptors in vivo.