Differential Regulation of the Myosin Heavy Chain Genes α and β in Rat Atria and Ventricles: Role of Antisense RNA

Background: The myosin heavy chain (MHC) genes are regulated by triiodothyronine (T3) in a reciprocal and chamber-specific manner. To further our understanding of the potential mechanisms involved, we determined the T3 responsiveness of the MHC genes, α and β, and the β-MHC antisense (AS) gene in the rat ventricles and atria. Methods: Hypothyroid rats were administered a single physiologic (1 μg) or pharmacologic (20 μg) dose of T3, and sequential measurements of β-MHC hn- and AS RNA and α-MHC heterogeneous nuclear RNA from rat ventricular and atrial myocardium were performed with reverse transcription PCR. Results: We have demonstrated that T3 treatment increases the myocyte content of an AS β-MHC RNA in atria and ventricles that includes sequences complementary to both the first 5′ and last 3′ introns of the β-MHC sense transcript. In the hypothyroid rat ventricle, β-MHC sense RNA expression is maximal, while in the euthyroid rat ventricle, β-MHC AS RNA is maximal. β-MHC AS expression increased by 52 ± ...