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La regulación de la salida del comportamiento circadiano a través de un circuito MicroRNA-JAK/STAT
1Cell and Molecular Biology Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cell
|February 7, 2012
Resumen
El microARN miR-279 controla los ritmos diarios de descanso: actividad en las moscas de la fruta mediante la regulación de la vía JAK / STAT, actuando aguas abajo del reloj circadiano central para influir en el comportamiento.
Área de la Ciencia:
- Cronobiología cronobiología.
- Biología Molecular Biología Molecular
- La neurociencia es la neurociencia.
Sus antecedentes:
- Se conocen los mecanismos moleculares de los relojes circadianos, pero aún no está claro cómo generan comportamientos rítmicos.
- Comprender la transmisión de señales desde el reloj circadiano es crucial para explicar los ritmos conductuales.
Objetivo del estudio:
- Para investigar el papel del microARN miR-279 en la regulación de los ritmos circadianos y el comportamiento en Drosophila.
- Para dilucidar la vía molecular a través de la cual miR-279 influye en los patrones de reposo:actividad.
Principales métodos:
- Manipulación genética de la expresión de miR-279 (sobreexpresión y deleción) en Drosophila.
- Análisis del descanso:ritmos de actividad y comportamiento circadiano.
- Investigación de la vía de señalización JAK/STAT, incluyendo el ligando Upd.
- Examen de la relación entre las neuronas del reloj y las neuronas que expresan Upd.
Principales resultados:
- miR-279 regula la señalización JAK/STAT para impulsar los ritmos de reposo y actividad de Drosophila.
- La alteración de los niveles de miR-279 (sobreexpresión o eliminación) interrumpe estos ritmos.
- miR-279 actúa aguas abajo del reloj circadiano central, ya que las oscilaciones de la proteína PERIOD permanecen normales.
- El ligando JAK/STAT Upd es un objetivo directo de miR-279; su knockdown rescata los fenotipos mutantes de miR-279.
- La modulación de la vía JAK/STAT afecta los ritmos circadianos, y las neuronas del reloj central pueden interactuar físicamente con las neuronas que expresan Upd.
Conclusiones:
- El microARN miR-279 es un regulador clave de los ritmos circadianos de reposo:actividad en Drosophila.
- La vía miR-279/JAK/STAT proporciona un mecanismo para que el reloj circadiano central controle el comportamiento.
- Este estudio revela un nuevo vínculo entre los microARN, la vía JAK / STAT y la generación del ritmo circadiano.
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