EXPRESSION OF THE THYROID-HORMONE RECEPTOR GENE, ERBA-ALPHA, IN B-LYMPHOCYTES - ALTERNATIVE MESSENGER-RNA PROCESSING IS INDEPENDENT OF DIFFERENTIATION BUT CORRELATES WITH ANTISENSE RNA LEVELS

The erbA alpha gene encodes two alpha-thyroid hormone receptor isoform s, TR alpha 1 and TR alpha 2, which arise from alternatively processed mRNAs, erbA alpha 1 (alpha 1) and erb alpha 2 (alpha 2). The splicing and alternative polyadenylation patterns of these mRNAs resemble that of mRNAs encoding different forms of immunoglobulin heavy chains, whi ch are regulated at the level of alternative processing during B cell differentiation, This study examines the levels of erbA alpha mRNA in eight B cell lines representing four stages of differentiation in orde r to determine whether regulation of the alternatively processed alpha 1 and alpha 2 mRNAs parallels the processing of immunoglobulin heavy chain mRNAs, Results show that the pattern of alpha 1 and alpha 2 mRNA expression is clearly different from that observed for immunoglobulin heavy chain mRNAs, B cell lines display characteristic ratios of alph a 1/alpha 2 mRNA at distinct stages of differentiation. Furthermore, e xpression of an overlapping gene, Rev-ErbA alpha (RevErb), was found t o correlate strongly with an increase in the ratio of alpha 1/alpha 2 mRNA, These results suggest that alternative processing of erbA alpha mRNAs is regulated by a mechanism which is distinct from that regulati ng immunoglobulin mRNA, The correlation between RevErb and erbA alpha mRNA is consistent with negative regulation of alpha 2 via antisense i nteractions with the complementary RevErb mRNA.