A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit.
A cDNA encoding a novel member of the thyroid/steroid hormone receptor superfamily, called Rev-ErbA alpha, has been isolated from a rat GH3 cell library. Rev-ErbA alpha is an approximately 56-kilodalton protein most similar in structure to the thyroid hormone receptor (c-erbA) and the retinoic acid receptor, but it does not bind either thyroid hormone or retinoic acid. The mRNA encoding Rev-ErbA alpha is present in many tissues and is particularly abundant in skeletal muscle and brown fat. A genomic DNA fragment containing the entire Rev-ErbA alpha cDNA sequence was isolated and characterized. Remarkably, this DNA fragment also contained a portion of the c-erbA alpha gene. r-erbA alpha-1 and r-erbA alpha-2 are alternative splice products of the c-erbA alpha gene and are members of the receptor superfamily. The genes encoding Rev-ErbA alpha and r-erbA alpha-2 overlap, with their coding strands oriented opposite one another. A 269-base-pair segment of the bidirectionally transcribed region is exonic in both the Rev-ErbA alpha and r-erbA alpha-2 genes, resulting in complementary mRNAs. Thus, through alternative splicing and opposite-strand transcription, a single genomic locus codes for three different members of the thyroid/steroid hormone receptor superfamily. Potential implications of this unusual genomic arrangement are discussed.
Lazar
M A
MA
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Hodin
R A
RA
Darling
D S
DS
Chin
W W
WW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011987:Receptors, Steroid / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D014158:Transcription, Genetic
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D004247:DNA