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La ARN polimerasa III detecta el ADN citosólico e induce interferones tipo I a través de la vía RIG-I
Yu-Hsin Chiu1, John B Macmillan, Zhijian J Chen
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Cell
|July 28, 2009
Resumen
El ADN citosólico desencadena una respuesta al interferón al ser convertido en ARN 5'-trifosfato (5'-ppp ARN) a través de la ARN polimerasa III (Pol-III). Este ARN luego activa la vía RIG-I, destacando el Pol-III.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Virología Virología.
Sus antecedentes:
- Los interferones tipo I (IFN) son cruciales para las respuestas antivirales y autoinmunes.
- La vía RIG-I/MAVS media la producción de IFN en respuesta al ARN citosólico.
- El mecanismo por el cual el ADN citosólico induce el IFN-beta era desconocido hasta ahora.
Objetivo del estudio:
- Para dilucidar el mecanismo de la inducción de IFN-beta por el ADN de doble cadena citosólico.
- Para identificar la enzima responsable de detectar el ADN citosólico e iniciar la respuesta IFN.
Principales métodos:
- Purificación bioquímica para identificar la enzima responsable.
- Transfección con ADN (poly(dA-dT)) y infección con virus de ADN.
- La inhibición de la actividad de la ARN polimerasa III (Pol-III).
- Infección con bacterias intracelulares (Legionella pneumophila).
Principales resultados:
- El ADN citosólico (poli-ADT) se convierte en ARN 5 -ppp.
- La ARN polimerasa III (Pol-III) dependiente del ADN sintetiza este ARN de 5 -ppp a partir de plantillas de ADN.
- La inhibición de Pol-III bloquea la inducción de IFN-beta por la transfección del ADN, los virus del ADN y la Legionella pneumophila.
- La inhibición de Pol-III mejora el crecimiento de Legionella pneumophila.
Conclusiones:
- La ARN polimerasa III actúa como un sensor de ADN citosólico.
- La conversión del ADN en ARN 5 -ppp por Pol-III es un paso clave en la detección inmune innata del ADN citosólico.
- Esta vía es crítica para controlar el virus del ADN y las infecciones bacterianas intracelulares.
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