Lee S L, Stewart K, Goodman R H
Division of Molecular Medicine, New England Medical Center Hospitals, Boston, Massachusetts 02111.
J Biol Chem. 1988 Nov 15;263(32):16604-9.
The gene encoding the hypothalamic peptide thyrotropin releasing hormone (TRH) was isolated from two rat genomic bacteriophage libraries. Southern blot analysis indicates that the gene is present as a single copy in the rat genome. The transcriptional unit is 2.6 kilobases in size and contains three exons interrupted by two introns of approximately 750 and 450 base pairs. Exon 1 encodes the 5'-untranslated region of the mRNA, exon 2 encodes the signal sequence and the majority of the amino-terminal peptide, and exon 3 encodes the remainder of the amino-terminal peptide, five copies of the TRH sequence, the carboxyl-terminal peptide, and the 3'-untranslated region of the mRNA. The general structure of the TRH gene resembles that of three other polypeptide hormone genes, preproopiomelanocortin, preproenkephalin A, and preproenkephalin B. Further sequence analysis revealed that characteristic promoter elements are present in the 5'-flanking region of the TRH gene. In addition, sequence homologies with the glucocorticoid receptor binding site, the GC box hexanucleotide, and a portion of the flanking region of the thyroid stimulating hormone beta-subunit gene were also identified. These upstream sequences may be important for the regulation of TRH gene expression.
编码下丘脑肽促甲状腺激素释放激素（TRH）的基因是从两个大鼠基因组噬菌体文库中分离出来的。Southern印迹分析表明该基因在大鼠基因组中以单拷贝形式存在。转录单位大小为2.6千碱基，包含三个外显子，被两个分别约为750和450碱基对的内含子打断。外显子1编码mRNA的5'-非翻译区，外显子2编码信号序列和大部分氨基末端肽，外显子3编码氨基末端肽的其余部分、TRH序列的五个拷贝、羧基末端肽以及mRNA的3'-非翻译区。TRH基因的总体结构与其他三个多肽激素基因——阿黑皮素原、脑啡肽原A和脑啡肽原B的结构相似。进一步的序列分析表明，TRH基因的5'-侧翼区存在特征性启动子元件。此外，还鉴定出与糖皮质激素受体结合位点、GC盒六核苷酸以及促甲状腺激素β亚基基因侧翼区一部分的序列同源性。这些上游序列可能对TRH基因表达的调控很重要。
