Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone.

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Abstract
The nucleotide and predicted amino acid sequences of two variant cDNAs [rat brain thyroid hormone receptor (rTR.alpha.) vI and vII], isolated from a rat brain cDNA library by using the Pst I fragment of v-erbA, showed virtual identity with the rat brain thyroid hormone receptor (rTR.alpha.) [Thompson, C. C., Weinberger, C., Lebo, R. and Evans, R. M. (1987) Science 237, 1610-1614] in the putative DNA binding domain and in the first 180 amino acids of the hormone binding domain but no similarity except for 5 amino acids at the extreme 3'' end. Isolation and sequencing of the 3'' end of the gene coding for rTR.alpha., vI and vII mRNAs revealed that the 3'' heterogeneity is due to alternative splicing of the primary transcripts of the same gene. RNA transfer blot analyses with probes unique to rTR.alpha., rTR.alpha. vI, and rTR.alpha. vII showed that only the variant mRNAs are abundantly expressed in rat brain, contrary to the previously reported high-level expression of rTR.alpha.. Since in vivo translation products of rTR.alpha. vI and rTR.alpha. vII did not bind thyroid hormones specifically, our findings explain the discrepancy between the reported abundance of the receptor mRNA and the low receptor levels determined by ligand binding studies in rat brain. These variant mRNAs are also expressed in kidney, heart, spleen, and liver, albeit at lower levels. The presence of an intact DNA binding domain in rTR.alpha. vI and rTR.alpha. vII suggests that the variants might have modulating functions in thyroid hormone action.