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Bases estructurales del retroceso, detención y reactivación de la ARN polimerasa II
Alan C M Cheung1, Patrick Cramer
1Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
Nature
|February 25, 2011
Resumen
El retroceso de la ARN polimerasa II (Pol II) detiene la transcripción. El factor de transcripción IIS (TFIIS) reactiva Pol II induciendo la escisión del ARN, un proceso crucial para la supervivencia celular y la regulación génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
- Reglamento genético Reglamento genético.
Sus antecedentes:
- La ARN polimerasa II (Pol II) transcribe el ADN en ARNm pero puede detenerse debido al retroceso.
- El arresto de Pol II detiene la transcripción, lo que requiere la reactivación por el factor de transcripción IIS (TFIIS) para la viabilidad celular.
- Estos procesos son críticos para navegar por los nucleosomas y regular la expresión génica cerca de los promotores.
Objetivo del estudio:
- Para aclarar los mecanismos estructurales que subyacen Pol II retroceso, arresto y reactivación mediada por TFIIS.
- Proporcionar un marco estructural para la comprensión del control de la elongación de la transcripción.
Principales métodos:
- Se empleó cristalografía de rayos X para determinar las estructuras de los complejos Pol II detenidos.
- Las estructuras se resolvieron a una resolución de 3,3 Å, incluido un complejo de Saccharomyces cerevisiae Pol II detenido con ADN y ARN.
- También se caracterizó estructuralmente un complejo intermedio de reactivación que contiene Pol II, ADN, ARN y TFIIS.
Principales resultados:
- El complejo detenido reveló que el ARN retrocedido ocupaba un "sitio de retroceso", atrapando el bucle de activación e inhibiendo el alargamiento.
- En el intermedio ligado al TFIIS, el TFIIS reubica el bucle de activación, desplaza el ARN y potencialmente facilita la escisión del ARN.
- Se identificó un residuo de "tirosina de entrada", que probablemente limita la extensión del retroceso del ARN.
Conclusiones:
- El estudio establece la base estructural detallada para el retroceso de Pol II, el arresto y la reactivación dependiente de TFIIS.
- Estos hallazgos ofrecen información sobre cómo se regula el alargamiento de la transcripción en secuencias específicas de ADN y durante la expresión génica.
- El marco estructural facilita un mayor análisis de la dinámica de la transcripción y su papel en los procesos celulares.
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