Expression of the Thyroid Hormone Receptor Gene, erbAα, in B Lymphocytes: Alternative mRNA Processing is Independent of Differentiation but Correlates with Antisense RNA Levels

The erbAα gene encodes two α-thyroid hormone receptor isoforms, TRα1 and TRα2, which arise from alternatively processed mRNAs, erbAα1 (α1) and erb α2 (α2). 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 erbAα mRNA in eight B cell lines representing four stages of differentiation in order to determine whether regulation of the alternatively processed α1 and α2 mRNAs parallels the processing of immunoglobulin heavy chain mRNAs. Results show that the pattern of α1 and α2 mRNA expression is clearly different from that observed for immunoglobulin heavy chain mRNAs. B cell lines display characteristic ratios of α1/α2 mRNA at distinct stages of differentiation. Furthermore, expression of an overlapping gene, Rev-ErbAα (RevErb), was found to correlate strongly with an increase in the ratio of α1/α2 mRNA. These results suggest that alternative processing of erbAα mRNAs is regulated by a mechanism which is distinct from that regulating immunoglobulin mRNA. The correlation between RevErb and erbAα mRNA is consistent with negative regulation of α2 via antisense interactions with the complementary RevErb mRNA