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El factor de transcripción GATA4 regula el empalme específico del tipo de célula a través de la interacción directa

Lili Zhu^1,2, Krishna Choudhary¹, Barbara Gonzalez-Teran^1,2

¹Gladstone Institutes, San Francisco, CA (L.Z., K.C., B.G-T., Y-S.A., R.T., N.R.S., L.L., P.Z., Y.H., A.P., F.K., A.P., N.S., A.H., M.W.C., C.A.G., J.G.v.B., R.H., B.R.C., B.G.B., N.J.K., K.S.P., D.S.).

|August 8, 2022

Resumen

GATA4 (proteína de unión a GATA 4) regula el empalme de ARN específico de la célula en las células del corazón mediante la unión del ARN y el espliceosoma. Este hallazgo revela un nuevo papel para GATA4 en el desarrollo y la enfermedad cardíaca.

Área de la Ciencia:

Biología cardiovascular
Biología molecular
Regulación genética

Sus antecedentes:

GATA4 (proteína de unión a GATA 4) es crucial para el desarrollo y la función del corazón.
Los defectos de empalme alternativos están relacionados con enfermedades cardíacas, pero su regulación en el corazón se entiende mal.

Objetivo del estudio:

Investigar el papel de GATA4 en el empalme alternativo específico del tipo de célula en progenitores cardíacos humanos.
Para descubrir los mecanismos moleculares por los cuales GATA4 regula el empalme.

Principales métodos:

Se utilizó la purificación de afinidad, la espectrometría de masas y el enlace cruzado mejorado con la inmunoprecipitación (eCLIP).
Se han realizado ensayos de desplazamiento electroforético (EMSA) y ensayos de empalme in vitro.
Realizó análisis transcriptómicos y experimentos de eliminación de GATA4.

Principales resultados:

GATA4 interactúa con los componentes del espliceosoma y se une directamente a numerosos ARNm a través de motivos específicos de ARN.
GATA4 regula el empalme alternativo, produciendo isoformas de proteínas funcionalmente distintas.
GATA4 knockdown altera el empalme de genes involucrados en la organización del citoesqueleto y el transporte de iones de calcio.

Conclusiones:

GATA4 funciona como un regulador de empalme a través de la unión directa al ARN, además de su papel transcripcional.
El empalme regulado por GATA4 afecta a los genes asociados con la miocardiopatía dilatada, lo que sugiere un papel novedoso en la homeostasis y la enfermedad cardíaca.

Palabras clave:

Factor de transcripción GATA4 El empalme de ARN Motivos de unión al ARN células madre pluripotentes inducidas Miocitos cardíacos

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