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¿Una hipótesis de ceRNA: la piedra de Rosetta de un lenguaje de ARN oculto?
Leonardo Salmena1, Laura Poliseno, Yvonne Tay
1Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cell
|August 2, 2011
Resumen
Los ARN mensajeros, los pseudogenes y los ARN largos no codificantes forman una red de ARN endógeno (ceRNA) competitivo. Esta red reguladora de todo el transcriptoma utiliza elementos de respuesta de microARN (MREs) e impacta en enfermedades como el cáncer.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La genómica es la genómica.
- ARN Biología Biología ARN
Sus antecedentes:
- El genoma humano contiene diversas moléculas de ARN más allá de los ARN mensajeros codificadores de proteínas (ARNm).
- Los ARN largos no codificantes (ARNlnc) y los pseudogenes transcritos representan porciones significativas del transcriptoma con funciones en gran medida desconocidas.
- Los microARN (miRNA) son reguladores clave de la expresión génica, principalmente a través de la unión a los elementos de respuesta de miRNA (MREs).
Objetivo del estudio:
- Proponer una hipótesis unificadora para las interacciones reguladoras entre los ARNm, los ARNm lnc y los pseudogenes.
- Introducir el concepto de competencia de la actividad del ARN endógeno (ceRNA) como un nuevo mecanismo regulador.
- Para resaltar el papel potencial de las redes de ceRNA en las enfermedades humanas, en particular el cáncer.
Principales métodos:
- Este estudio es principalmente un marco teórico basado en hipótesis.
- Integra el conocimiento existente de las interacciones ARN-ARN y la regulación del miARN.
- El concepto de MRE como un lenguaje compartido para la comunicación de ARN es central para la hipótesis.
Principales resultados:
- Los ARN mensajeros, los pseudogenes transcritos y los ARN largos no codificantes pueden interactuar a través de ERM compartidos.
- Esta interacción forma una red reguladora de RNA endógeno (ceRNA) competitivo a gran escala a través del transcriptoma.
- La actividad de ceRNA expande significativamente la información genética funcional codificada dentro del genoma humano.
Conclusiones:
- La hipótesis del ceRNA proporciona un nuevo marco para la comprensión de la regulación post-transcripcional.
- Las redes de ceRNA representan una capa reguladora generalizada con implicaciones sustanciales para la función celular.
- La desregulación de las redes de ceRNA está implicada en la patogénesis de varias enfermedades, incluido el cáncer, ofreciendo objetivos terapéuticos potenciales.
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