Schematic representation of TRH synthesis. (A) The primary transcript is synthesized in the nucleus as prepro-TRH heterogeneous nuclear RNA (hnRNA) which contains two introns and three exons. (B) After splicing, mature RNA is transported to the cytosol, binds to ribosomes, begins transcription of prepro-TRH mRNA, the leader sequence is cleaved, synthesis of pro-TRH continues with ribosomes linked to rough endoplasmic reticulum (RER) and precursor is transported inside the ER. (C) At the transGolgi pro-TRH may suffer a first cleavage by protein convertase 1 (PC1), proTRH is compartamentalized in secretory granules with the rest of processing enzymes: PCs cleave at the carboxy end of a pair of basic residues, a carboxypeptidase cleaves the basic residues leaving the immediate precursor of TRH: gln–his–progly (black squares) and cryptic peptides (green); pyroglutaminase converts gln to pyroglu and peptidylglycine-α-amidase (PAM) leaves the amino group of the glycine bound to the carboxyl end (forming the amide group) and cleaves the rest of the procarbon moieties. Processing occurs as the secretory granule is transported to the nerve terminal (Nillni 2010).
Citation: Journal of Endocrinology 227, 3; 10.1530/JOE-14-0593e