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Hsp90 se dirige globalmente a la ARN polimerasa en pausa para regular la expresión génica en respuesta a los
Ritwick Sawarkar1, Cem Sievers, Renato Paro
1Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Cell
|May 15, 2012
Resumen
La proteína de choque térmico 90 (Hsp90) estabiliza la pausa de la ARN polimerasa II, optimizando la expresión génica. Esta chaperona es crucial para la activación de genes en respuesta a los cambios ambientales, que afectan la salud y la evolución.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La proteína de choque térmico 90 (Hsp90) es un acompañante molecular vital para la maduración de las proteínas.
- Hsp90 influye en el desarrollo, el cáncer y los procesos evolutivos.
Objetivo del estudio:
- Para investigar los sitios de unión a la cromatina de todo el genoma de Hsp90 en Drosophila.
- Para aclarar el papel de Hsp90 en la orquestación de la fisiología celular y la regulación génica.
Principales métodos:
- Mapeo de alta resolución de los sitios de unión a la cromatina Hsp90 en todo el genoma de Drosophila.
- Análisis computacionales y bioquímicos para determinar la interacción de Hsp90 con promotores de genes y complejos reguladores.
- Estudios de inhibición en Drosophila y células de mamíferos para evaluar el impacto en la expresión génica.
Principales resultados:
- Hsp90 se localiza cerca de promotores de genes codificantes y no codificantes, incluidos los microARN.
- Hsp90 estabiliza el complejo del factor de alargamiento negativo (NELF), manteniendo y optimizando la pausa de la ARN polimerasa II.
- La inhibición de Hsp90 conduce a la regulación al alza del gen objetivo; Hsp90 es esencial para la activación máxima de los genes en pausa.
Conclusiones:
- Hsp90 juega un papel inesperado en la regulación de la expresión génica a través de la pausa de la ARN polimerasa II.
- Este mecanismo tiene amplias implicaciones para las funciones de Hsp90 en la fisiología celular, la salud, las enfermedades y la evolución.
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