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La regulación del receptor de la hormona nuclear de los microARN controla la progresión del desarrollo
Axel Bethke1, Nicole Fielenbach, Zhu Wang
1Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Science (New York, N.Y.)
|April 4, 2009
Resumen
Los receptores nucleares y los microARN controlan la expresión génica durante el desarrollo. Este estudio revela cómo el receptor nuclear DAF-12 utiliza microARN como un interruptor molecular para la transición entre las etapas de desarrollo en respuesta a las hormonas.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Endocrinología Molecular La Endocrinología Molecular
- Regulación genética Reglamento genético.
Sus antecedentes:
- Los receptores nucleares (RN) regulan la expresión génica en respuesta a pequeñas moléculas como los retinoides y los esteroides, controlando el desarrollo de los tejidos.
- Los microARN (miRNA) son pequeños ARN no codificantes que regulan la expresión génica post-transcripcionalmente y son cruciales en el desarrollo y la enfermedad.
Objetivo del estudio:
- Para investigar el papel del receptor nuclear DAF-12 de Caenorhabditis elegans en la regulación de la expresión del microARN.
- Aclarar el mecanismo por el cual DAF-12 y su ligando controlan las transiciones del desarrollo a través de microARN.
Principales métodos:
- Análisis del receptor nuclear DAF-12 de Caenorhabditis elegans y su ligando esteroide.
- Investigó la activación de los promotores de la familia de microARN let-7.
- Estudió la regulación a la baja del gen diana del microARN hbl-1 y su efecto en los patrones de división celular.
Principales resultados:
- El receptor nuclear DAF-12, al unirse a su ligando esteroide, activa directamente los promotores de los miembros de la familia de microARN let-7.
- Esta activación conduce a la regulación a la baja del microARN blanco hbl-1, que está involucrado en la progresión de las células madre epidérmicas.
- En ausencia del ligando, DAF-12 reprime la expresión de microARN, lo que se correlaciona con la detención del desarrollo.
Conclusiones:
- Los microARN funcionan como componentes de un interruptor molecular acoplado a una hormona.
- Este mecanismo de interrupción permite la terminación de programas de desarrollo anteriores para permitir el inicio de los posteriores.
- Identifica una nueva vía reguladora que vincula la señalización de la hormona nuclear con el tiempo de desarrollo mediado por microARN.
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