Regulation of expression of the alternative mRNAs of the rat alpha-thyroid hormone receptor gene.

The rat alpha-thyroid hormone receptor gene encodes through alternative splicing at least three protein isoforms with different functions, and three mRNA species (2.6, 5.4, 6.8 kilobase (kb) in size) are detected using alpha gene-specific probes (Mitsuhashi, T., Tennyson, G. E., Nikodem, V. M. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 5804-5808). In the present study, the identities of these mRNAs were analyzed by Northern analysis, and it was demonstrated that in rat brain the receptor protein is encoded by the minor 5.4- and 6.8-kb mRNAs and the variant proteins are encoded by the major 2.6-kb mRNA. Relative quantities of these mRNAs were determined by RNase protection assay, and the ratio of the receptor mRNAs to the variant mRNAs was estimated to be 1:6 in adult brain. The ratio between the mRNAs was regulated in both a tissue-specific and developmental stage-specific manner. The receptor mRNA levels were also regulated by the thyroid state of the animal showing an increased level in hypothyroid rat liver while those in brain were not affected. Analysis of the alpha-thyroid hormone receptor gene suggested that the choice between two poly-adenylation sites and subsequent RNA processing appear to generate the 3' heterogeneity of these alternative mRNAs.