Rapid induction of a specific nuclear mRNA precursor by thyroid hormone.

Administration of thyroid hormone to the thyroidectomized rat results in a rapid and dramatic increase in the relative amount of hepatic mRNA coding for spot 14--a translational product with an approximate Mr of 17,500 and isoelectric point of 4.9. We have now isolated a cDNA clone containing sequences homologous to this thyroid hormone-responsive mRNA. Two distinct mRNA species that differed by 200 nucleotides in length were found to be capable of hybridizing to the cDNA probe. Both mRNA species were proportionally elevated in relative concentration in rats with increasing plasma levels of thyroid hormone. The earliest change in the levels of mature mRNA occurred at 20 minutes following thyroid hormone treatment of the thyroidectomized rat. Analysis of nuclear RNA revealed a single higher molecular weight species that was homologous to spot 14 mRNA. An increase in the nuclear level of this putative precursor occurred by 10 minutes following thyroid hormone administration, a time preceding the earliest change in mature mRNA. Thus, thyroid hormone appears to act at least in part at a nuclear level in altering the cellular concentration of this mRNA species. The rapidity of this change suggests that it may reflect a direct response to the binding of thyroid hormone to its nuclear receptor.