Expression of the thyroid hormone receptor gene, erbAalpha, in B lymphocytes: alternative mRNA processing is independent of differentiation but correlates with antisense RNA levels.

Abstract

The erbAalpha gene encodes two alpha-thyroid hormone receptor isoforms, TRalpha1 and TRalpha2, which arise from alternatively processed mRNAs, erbAalpha1 (alpha1) and erb alpha2 (alpha2). The splicing and alternative polyadenylation patterns of these mRNAs resemble that of mRNAs encoding different forms of immunoglobulin heavy chains, which are regulated at the level of alternative processing during B cell differentiation. This study examines the levels of erbAalpha mRNA in eight B cell lines representing four stages of differentiation in order to determine whether regulation of the alternatively processed alpha1 and alpha2 mRNAs parallels the processing of immunoglobulin heavy chain mRNAs. Results show that the pattern of alpha1 and alpha2 mRNA expression is clearly different from that observed for immunoglobulin heavy chain mRNAs. B cell lines display characteristic ratios of alpha1/alpha2 mRNA at distinct stages of differentiation. Furthermore, expression of an overlapping gene, Rev-ErbAalpha (RevErb), was found to correlate strongly with an increase in the ratio of alpha1/alpha2 mRNA. These results suggest that alternative processing of erbAalpha mRNAs is regulated by a mechanism which is distinct from that regulating immunoglobulin mRNA. The correlation between RevErb and erbAalpha mRNA is consistent with negative regulation of alpha2 via antisense interactions with the complementary RevErb mRNA.