Abstract 12447: MicroRNA 26b Encoded by the Intron of Small CTD Phosphatases (SCPs) 1 Has an Antagonistic Effect on its Host Gene and Suppresses Cardiac Hypertrophy
Tissue-specific and developmental pattern of gene expression plays an important role in distinctive features of each organ. Expression of a family of class-C RNA polymerase II (RNAPII) carboxyl-terminal domain (CTD) phosphatases [small CTD phosphatases (SCPs) 1 to 3] is restricted to non-neuronal tissues. SCP 1 to 3 are recruited by the repressor element 1 (RE-1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. SCPs are highly expressed in the heart and contain microRNA (miR)-26b, 26a-2, and 26a-1 in their introns, implying their important functions in cardiomyocytes. Therefore, we tried to investigate the roles of these miRs and their host genes in neonatal rat cardiomyocytes.Overexpression of SCP1 by lentivirus induced the mRNA expressions of ANF and βMHC and increased cell surface area in cardiomyocytes. Moreover, suppression of SCP1 by tranducing RNAi against SCP1 reduced these gene expressions and suppressed cardiomyocyte hypertrophy. On the other hand, overexpression of miR-26b suppressed the mRNA expressions of ANF and βMHC and reduced cell surface area in cardiomyocytes. We confirmed that miR-26 family targets the 3'UTR of GATA4 and canonical transient receptor potential channel (TRPC) 3 by luciferase assay. Overexpression of miR-26b in cardiomyocytes reduced the expressions of TRPC3 and GATA4. Conversely, silencing of endogenous miR-26b family by transduction of ‘decoy’ gene, which has 6-tandem repeats of antisense sequence of miR-26b downstream of luciferase gene, enhanced the expressions of TRPC3 and GATA4. Thus, SCPs 1 to 3 not only repress neuron-specific genes but also inhibit hypertrophic responses thorough their intronic miR-26b, 26a-2, and 26a-1 in cardiomyocytes. The coregulation of a miRNA with its host gene typically exhibits one of two main functions: (i) an antagonistic effect by miRNA mediated knock-down of genes with perturbing effects on a pathway or a biological process activated by the host gene, or (ii) a synergistic effect by miRNA-mediated fine tuning of a target gene generating a positive effect on the host gene. In this case, miR-26b has an antagonistic effect on its host gene SCP1.
- © 2011 by American Heart Association, Inc.