Regulation of antisense RNA expression during cardiac MHC gene switching in response to pressure overload

Abstract

pertension has been shown to cause cardiac hypertrophy and a shift in myosin heavy chain (MHC) gene expression from the faster - to slower -MHC isoform. The expression of the - and -MHC pre-mRNAs, mRNAs, as well as the newly discovered antisense -RNA were analyzed in three regions of the normal control (NC) and 12-day pressure-overloaded (AbCon) hearts: the left ventricle apex, left ventricle base, and the septum. The RNA analyses in the AbCon heart targeted both the 5 and the 3 ends of each RNA molecule. -MHC mRNA expression significantly increased relative to control in all three regions, regardless of the target site (5 or 3 end). In contrast, -MHC pre-mRNA expression in the AbCon heart depended on the site of the measurement (5 vs. 3 end). For example, whereas the pre-mRNA did not change when targeted at the 3 end (last intron), it increased significantly in the AbCon heart when measure-ment targeted the 5 end (2nd intron) of the 25-kb molecule. Analyse