title: Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain.
abstract: We amplified human thyroidal cDNA using oligonucleotide primers designed to reveal putative human thyrotropin receptor (hTSHR) mRNA variants encoding the extracellular, ligand-binding domain but lacking the transmembrane domain. Whereas the major 4.3 kb hTSHR mRNA species was not amplified to detectable levels, several shorter products were detected. A strongly amplified 1 kb product was cloned and sequenced. It contained coding sequences at the 5' end which were colinear with exons 1-8 of the hTSHR gene, encoding most of the extracellular domain. This was followed at the 3' end by additional coding and noncoding information not present in the 4.3 kb transcript. A probe specific for the 5' end recognized polyadenylated thyroidal transcripts of 4.3, 1.7, and 1.3 kb, indicating the presence of several hTSHR mRNA variants. A probe specific for the 3' end recognized only the 1.3 kb transcript. The level of the 1.3 kb variant (hTSHR-v 1.3 mRNA) was about half that of the 4.3 kb hTSHR mRNA and twice that of the 1.7 kb variant. The presence of a thyroidal mRNA encoding both the signal peptide and ligand-binding region of the hTSHR, but not the seven transmembrane helices, provides the potential to produce soluble receptors which could play important roles in thyroid physiology and/or autoimmune thyroid disease.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
authors.forename: P N
authors.initials: PN
authors.lastname: Graves
authors.forename: Y
authors.initials: Y
authors.lastname: Tomer
authors.forename: T F
authors.initials: TF
authors.lastname: Davies
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry; D014644:Genetic Variation; D006111:Graves Disease / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000737:chemistry / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013961:Thyroid Gland / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D004247:DNA