Characterization of the mouse thyrotrophin-releasing hormone receptor gene: an exon corresponds to a deletion in the rat cDNA

Abstract

The cloning and characterization of the mouse TRH receptor (TRH-R) gene revealed an untranslated exon (exon 1), a single intron and an upstream dinucleotide repeat sequence (d(TG)16.d(AG)21) in the 5' untranslated region (UTR). The coding region was contained almost entirely on a second exon (exon 2), with the final amino acid and stop codon at the COOH terminus of the gene encoded by a third exon (exon 3) flanked by two introns. The 3' UTR was contained on the remainder of exon 3 and on the final exon (exon 4). Exon 3 (228 bp) corresponds exactly to a 228 bp deletion that exists in the rat TRH-R cDNA, but not in the mouse cDNA. The mouse TRH-R cDNA encodes a protein of 393 amino acids which is 96% homologous to the rat TRH-R protein of 412 amino acids, but is 19 amino acids shorter at its COOH terminus. The coding sequence for these 19 amino acids (plus 1 extra amino acid) does exist in the mouse TRH-R gene, but the sequence is encoded by exon 4, separated from the rest of the coding region by the stop codon and 223 bp of 3' UTR on exon 3. Splicing of exon 3 in the mouse TRH-R gene would remove the last amino acid, the stop codon and the 223 bp of 3' UTR, allowing transcription to continue into the 3' UTR on exon 4, which encodes the 19 extra amino acids found in the rat cDNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Genomic Organization and Promoter Function of the Human Thyrotropin-releasing Hormone Receptor Gene

“…DISCUSSION We previously reported the existence of an intron in the coding region of the human TRHR gene based on its partial genomic sequence (17). The partial genomic sequence of the mouse TRHR has also recently been reported (13). However, the complete structure, including transcriptional start site, number of introns, and functional polyadenylation signals etc., has not been reported.…”

“…There are several d(TG) n dinucleotide repeats present in the 5Ј-region of the human TRHR gene, similar to the mouse TRHR gene (13). These repeats are often found in areas that serve as regulatory elements for gene expression and are thought to be potential Z-DNA-forming sequences.…”

“…Following cloning of the mouse TRHR cDNA by Straub et al (16), we and others have cloned a human pituitary TRHR cDNA and its partial genomic DNA (13)(14)(15)(16)(17). The deduced amino acid sequence from the cDNA revealed that TRHR is a member of the family of G protein-coupled receptors containing putative seven transmembrane domains.…”

Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor

“…These are TRH receptor 1 (TRH-R1), which is the primary (or only) receptor in TSH-secreting cells, and TRH-R2, which is expressed throughout the CNS along with TRH-R1 but typically in different areas of the brain (O’Dowd et al, 2000; Sun et al, 2003). In humans, by contrast, only a single type of receptor for TRH, TRH-R, is expressed that is more similar to TRH-R1 than TRH-R2 (Duthie et al, 1993; Matre et al, 1993). It has been reported that TAL binds with lower affinity than TRH to receptors in rat or mouse pituitary and in brain tissue preparations (Kinoshita et al, 1997; Asai et al, 1999, 2005).…”

Structural and Functional Organization of the Gene Encoding the Human Thyrotropin‐Releasing Hormone Receptor

“…The mapped intron 2 seemed at first to be a unique feature of the human TRHR as no intron was found in the ORF of the mouse and rat TRHR genes (de la Pena et al, 1992 b ; Duthie et al, 1993 ; Satoh et al, 1993 b ). To extend the evolutionary perspective of our finding, we set out to determine whether the large intron 2 of the TRHR gene was present in chimpanzee and sheep genomic DNA.…”