Isolation of a cDNA Encoding Human Rev-ErbAα: Transcription from the Noncoding DNA Strand of a Thyroid Hormone Receptor Gene Results in a Related Protein That Does Not Bind Thyroid Hormone

Abstract

A cDNA encoding Rev-ErbAα, a member of the thyroid/steroid hormone receptor superfamily, has been isolated from a human fetal skeletal muscle library. This cDNA contains 269 consecutive base pairs identical to a region of a human c-erbAα-2 cDNA, but the respective long open reading frames utilize this nucleotide sequence in opposite orientations. Thus, human Rev-ErbAα (hRev) is derived from opposite-strand transcription of the c-erbAα genomic locus. mRNA encoding hRev was detected in human skeletal muscle by Northern analysis. Comparison of hRev and Rev-ErbA (rRev) reveals 99% identity in the putative DNA-binding and "ligand-binding" (carboxy-terminal) domains. hRev does not bind thyroid hormone (T₃), as has also been found for its rat homolog. Interestingly, the human and rat Rev-ErbAα cDNAs are dissimilar at their 5′ ends, corresponding to the first exon that we have identified in the rat gene. The conservation of the bidirectionally transcribed regions of c-erbAα-2 and Rev-ErbAα in human and rat suggests that this unusual genomic arrangement has an important function, perhaps related to the regulation of gene expression.