Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6482
Caracterización de la función de SRSF3 en la homeostasis del corazón y en el infarto de miocardio
Ortiz-Sanchez, Paula CNIC
Lara-Pezzi, Enrique CNIC
Cardiovascular diseases are a major cause of mortality and hospitalization worldwide, however the role of RNA binding proteins (RBPs) in heart disease is poorly understood. We have found that SRSF3 expression decreases after myocardial infarction (MI), suggesting that it may play a role in cardiac homeostasis and/or disease. We found that SRSF3 cardiac depletion during development is embryonic lethal, indicating that SRSF3 is necessary for heart development, especially after E11.5 when its expression is upregulated in the heart. To determine the role of SRSF3 in the adult heart we developed a cardiomyocytespecific tamoxifen-inducible SRSF3 knockout mouse line. After tamoxifen injection, mice showed a dramatic reduction in heart contractility, resulting in death of the animal within eight days. Gene expression analysis showed increased expression of cardiac dysfunction markers, together with a downregulation of genes involved in cardiac contraction. We also found that SRSF3 interacts with LSM14A, which has been described to promote mRNA decapping and degradation. Interestingly, we observed increased decapping of those mRNAs downregulated after SRSF3 depletion. These results suggest that SRSF3 prevents mRNA decapping probably by interacting with LSM14A and that its depletion induces the degradation of contraction related genes due to decapping. Using an adeno-associated virus serotype 9 that overexpresses SRSF3 (AAV9-SRSF3), we observed that after MI, overexpression of SRSF3 resulted in an increase in left ventricular ejection fraction and a decrease in left ventricular diastolic volume, suggesting that the downregulation of SRSF3 after MI is partially responsible for the deterioration of cardiac function. Furthermore, we have also found increased decapping and downregulation of contraction related genes after MI in C57BL/6 mice.
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