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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Modulación del procesamiento del microARN por p53
Hiroshi I Suzuki1, Kaoru Yamagata, Koichi Sugimoto
1Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|July 24, 2009
Resumen
El supresor tumoral p53 mejora la maduración del microARN (miRNA) después del daño del ADN al interactuar con el complejo de Drosha. Esto revela un nuevo papel para p53 en la regulación de la biogénesis del miRNA y la supresión tumoral.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología del cáncer Biología del cáncer.
- ARN Biología Biología ARN
Sus antecedentes:
- Los microARN (miRNA) son reguladores de genes post-transcripcionales cruciales con funciones tanto en la promoción como en la supresión de tumores.
- La regulación a la baja de los miRNAs es común en los cánceres humanos, destacando su importancia supresora del tumor.
- La interacción entre las redes supresoras de tumores y la maquinaria de biogénesis de miRNA no se entiende completamente.
Objetivo del estudio:
- Para investigar la conexión entre el supresor tumoral p53 y la biogénesis de miRNA.
- Para determinar si p53 influye en el procesamiento de miRNAs supresores de tumores específicos.
- Para dilucidar el mecanismo por el cual p53 afecta la maduración del miRNA.
Principales métodos:
- Estudió el efecto de p53 en el procesamiento de miRNA en células HCT116 y fibroblastos diploides humanos.
- Investigó la interacción entre p53, el complejo de Drosha, y la helicasa p68 de ARN de la caja DEAD (DDX5).
- Se utilizaron mutantes p53 transcripcionalmente inactivos para evaluar el impacto en el procesamiento del miRNA.
Principales resultados:
- p53 mejora la maduración post-transcripcional de miRNAs supresores del crecimiento (por ejemplo, miR-16-1, miR-143, miR-145) en respuesta al daño del ADN.
- p53 se asocia con el complejo de procesamiento de Drosha a través de p68 (DDX5), facilitando el procesamiento del miRNA primario al miRNA precursor.
- Los mutantes p53 inactivos interrumpen el ensamblaje del complejo p53-p68-Drosha, perjudicando el procesamiento del miRNA.
Conclusiones:
- p53 juega un papel independiente de la transcripción en la modulación de la biogénesis del miRNA, parte integral de su función supresora del tumor.
- Esta función recientemente identificada de p53 en el procesamiento de miRNA ofrece información sobre la biología del cáncer.
- La regulación de p53 de la maduración del miRNA representa un vínculo crítico entre la respuesta al estrés celular y la supresión del tumor.
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