Lazar M A, Hodin R A, Darling D S, Chin W W
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Mol Cell Biol. 1989 Mar;9(3):1128-36. doi: 10.1128/mcb.9.3.1128-1136.1989.
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.
从大鼠GH3细胞文库中分离出一种编码甲状腺/类固醇激素受体超家族新成员的cDNA，称为Rev-ErbAα。Rev-ErbAα是一种分子量约为56千道尔顿的蛋白质，其结构与甲状腺激素受体（c-erbA）和视黄酸受体最为相似，但它既不结合甲状腺激素也不结合视黄酸。编码Rev-ErbAα的mRNA存在于许多组织中，在骨骼肌和褐色脂肪中尤其丰富。分离并鉴定了一个包含整个Rev-ErbAα cDNA序列的基因组DNA片段。值得注意的是，该DNA片段还包含c-erbAα基因的一部分。r-erbAα-1和r-erbAα-2是c-erbAα基因的可变剪接产物，属于受体超家族成员。编码Rev-ErbAα和r-erbAα-2的基因相互重叠，其编码链方向相反。双向转录区域的一个269个碱基对的片段在Rev-ErbAα和r-erbAα-2基因中均为外显子，产生互补的mRNA。因此，通过可变剪接和反向转录，一个单一的基因组位点编码甲状腺/类固醇激素受体超家族的三个不同成员。文中讨论了这种不寻常基因组排列的潜在影响。
