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El ARNS SRSF3 controla la formación epicárdica regulando el empalme y la proliferación
Irina-Elena Lupu1, Susann Bruche1, Anob M Chakrabarti2,3
1Institute of Developmental and Regenerative Medicine, British Heart Foundation Centre of Research Excellence, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX3 7TY, UK.
Development (Cambridge, England)
|January 28, 2026
Resumen
La proteína de unión a ARN SRSF3 es crucial para la formación epicárdica durante el desarrollo embrionario. Su deleción detiene la proliferación de células epicárdicas, afectando el desarrollo y la regeneración cardíaca.
Área de la Ciencia:
- Biología Cardiovascular
- Biología del Desarrollo
- Biología Molecular
Sus antecedentes:
- El epicardio juega un papel vital en el desarrollo y la regeneración del corazón.
- Los mecanismos moleculares clave que rigen la formación epicárdica siguen sin entenderse completamente.
Objetivo del estudio:
- Investigar el papel de la proteína de unión a ARN SRSF3 en la formación y función epicárdica.
- Elucidar los mecanismos moleculares subyacentes a la regulación del desarrollo epicárdico por SRSF3.
Principales métodos:
- Se utilizaron modelos murinos con deleción dirigida de Srsf3 en el proepicardio.
- Se empleó la secuenciación de ARN de célula única para analizar las respuestas celulares a la depleción de Srsf3.
- Se realizó irCLIP endógeno para mapear las interacciones ARN-SRSF3.
Principales resultados:
- La deleción de Srsf3 en el proepicardio murino causó detención proliferativa y alteración de la formación epicárdica.
- La depleción de Srsf3 condujo a una reducción de la proliferación epicárdica y la formación de células derivadas del epicardio (EPDC).
- SRSF3 se une a los reguladores del ciclo celular Ccnd1 y Map4k4, influyendo en sus funciones de empalme y no de empalme.
Conclusiones:
- SRSF3 es esencial para controlar la proliferación epicárdica y garantizar la formación epicárdica adecuada.
- SRSF3 regula el desarrollo cardíaco a través de mecanismos dependientes e independientes del empalme.
- La recombinación en mosaico puede confundir significativamente la fenotipificación embrionaria, lo que subraya la importancia del papel regulador de SRSF3.
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