Multifaceted roles of miR-1s in repressing the fetal gene program in the heart.

摘要: miRNAs are an important class of regulators that play roles in cellular homeostasis and disease. Muscle-specific miRNAs, miR-1-1 miR-1-2, have been found to regulating cell proliferation cardiac function. Redundancy between miR-1-2 has previously impeded a full understanding their vivo. To determine how miR-1s regulate function vivo, we generated mice lacking without affecting nearby genes. miR-1 double knockout (miR-1 dKO) were viable not significantly different from wild-type controls at postnatal day 2.5. Thereafter, all dKO developed dilated cardiomyopathy (DCM) died before P17. Massively parallel sequencing showed large portion upregulated genes after deletion is associated with the fetal gene program including proliferation, glycolysis, glycogenesis, sarcomere-associated Consistent profiling, glycogen content glycolytic rates increased mice. Estrogen-related Receptor β (Errβ) was identified as direct target miR-1, which can expression sarcomeric proteins. Cardiac-specific overexpression Errβ led storage, dilation, sudden death around 3-4 weeks age. We conclude its primary act together transition prenatal neonatal stages by repressing program. Loss this regulation leads DCM.