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El complejo TREX-2 asociado a los poros nucleares emplea un mediador para regular la expresión génica

Maren Schneider¹, Doris Hellerschmied², Tobias Schubert¹

¹Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.

|August 29, 2015

Resumen

El complejo TREX-2 interactúa con el complejo Mediator para regular la transcripción génica y la exportación de ARNm. Este hallazgo revela cómo los complejos de poros nucleares influyen en la expresión génica al conectar la transcripción y el procesamiento de ARN.

Área de la Ciencia:

Biología molecular
Biología celular
Regulación genética

Sus antecedentes:

Los complejos de poros nucleares (NPC) regulan el transporte entre el núcleo y el citoplasma.
El complejo TREX-2, ubicado en la canasta de NPC, influye en la expresión génica, la transcripción y la exportación de ARNm.
El mecanismo preciso por el cual TREX-2 regula la maquinaria de expresión génica sigue sin estar claro.

Objetivo del estudio:

Para aclarar el mecanismo por el cual el complejo TREX-2 regula la expresión génica.
Para investigar la interacción entre TREX-2 y el complejo Mediator, un regulador clave de la ARN polimerasa II (Pol II).

Principales métodos:

Estudios estructurales y bioquímicos para identificar las regiones de interacción de TREX-2 con Mediator.
Análisis del ensamblaje del complejo Mediator con la cinasa Cdk8.
Evaluación del reclutamiento y la fosforilación de Pol II.
Perfiles transcriptómicos y fenotípicos para evaluar la interdependencia de TREX-2 y Med31.
Investigación del papel de TREX-2 en la exportación de ARNm.

Principales resultados:

TREX-2 se une directamente al submódulo Mediador Med31/Med7N a través de una región conservada.
TREX-2 regula el ensamblaje del mediador con la cinasa Cdk8.
TREX-2 es esencial para el reclutamiento de Pol II y la fosforilación específica del sitio.
TREX-2 y Med31 muestran interdependencia funcional en genes específicos.
TREX-2 utiliza su superficie de interacción con el mediador para regular la exportación de ARNm, vinculando la transcripción y el procesamiento de ARNm.

Conclusiones:

TREX-2 actúa como un complejo adaptador que accede a la maquinaria de transcripción del núcleo a través del complejo Mediator.
TREX-2 integra la iniciación de la transcripción con las primeras etapas de procesamiento de ARNm.
Este estudio proporciona una visión mecanicista de cómo los factores asociados a las NPC regulan la expresión génica.

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