Thyrotropin regulates thyroglobulin mRNA splicing and differential processing.

Rat thyroid tissue and cultured rat thyrocyte lines contain two thyroglobulin (Tg) mRNAs: a 9 kb rTg-1 mRNA encoding the 330, kDa Tg monomer and a recently described 0.95 kb rTg-2 mRNA. These transcripts have identical 5' coding sequences (641 nucleotides); however, the 3' end of rTg-2 is comprised of coding and non-coding sequences not present in rTg-1. To determine if a single Tg gene encoded both mRNA species, a genomic clone was isolated which spanned the full-length rTg-2 cDNA sequence. The promoter sequence and restriction map were the same as for the previously characterized rTg-1 gene, indicating that rTg-1 and rTg-2 mRNAs are splicing variants derived from the same Tg gene. The unique 3' end of rTg-2 mRNA comprised a single exon which was intronic with respect to rTg-1 mRNA formation. The level of rTg-2 in cultured rat thyrocytes was more sensitive to thyrotropin (TSH) regulation than was rTg-1. rTg-2 mRNA was rapidly (and reversibly) depleted to nearly undetectable levels after TSH removal, unlike rTg-1. Conversely, TSH rapidly restored control levels of rTg-2 mRNA in such depleted cells. The data thus support a model of TSH-induced splicing and regulation of the two Tg mRNAs in the rat.