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Las proteínas SR colaboran con 7SK y el ARN naciente asociado al promotor para liberar la polimerasa en pausa
Xiong Ji1, Yu Zhou, Shatakshi Pandit
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Cell
|May 14, 2013
Resumen
SRSF2 libera la polimerasa II de la pausa proximal del promotor al unirse al ARN naciente. Esta acción libera P-TEFb, activando la transcripción y permitiendo la expresión génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
- ARN Biología Biología ARN
Sus antecedentes:
- Es común que la ARN polimerasa II (RNAP II) haga una pausa cerca de los promotores de genes de mamíferos.
- La transición a la elongación productiva requiere el reclutamiento de P-TEFb, una quinasa clave para la RNAP II.
- P-TEFb está parcialmente secuestrado en un complejo inhibidor con ARN no codificante 7SK, pero su mecanismo de liberación durante la activación de la transcripción no estaba claro.
Objetivo del estudio:
- Investigar el mecanismo de liberación de P-TEFb del complejo 7SK durante la activación de la transcripción.
- Determinar el papel de SRSF2 (SC35) en la liberación de la pausa de transcripción y la activación génica.
Principales métodos:
- Investigó la composición del complejo 7SK en promotores de genes.
- Evaluó la función de SRSF2 en la liberación de P-TEFb y la activación de la transcripción.
- Se analizó la interacción de SRSF2 con el ARN naciente asociado al promotor.
Principales resultados:
- SRSF2 es un componente del complejo 7SK en los promotores de genes.
- SRSF2 media la liberación coordinada y dependiente del ARN de SRSF2 y P-TEFb del complejo 7SK.
- La unión de SRSF2 al ARN naciente asociado al promotor desencadena la activación de la transcripción.
Conclusiones:
- SRSF2 juega un papel directo en la liberación de RNAP II desde la pausa proximal del promotor.
- El ARN naciente promotor-proximal es crucial para la activación de genes celulares.
- Un mecanismo análogo al Tat/TAR del VIH está involucrado en la activación de genes celulares.
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