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El RNAi promueve el silenciamiento heterocromático a través de la liberación acoplada a la replicación del ARN Pol II
Mikel Zaratiegui1, Stephane E Castel, Danielle V Irvine
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Nature
|October 18, 2011
Resumen
La interferencia del ARN (RNAi) es crucial para mantener la heterocromatina durante la división celular. En la levadura de fisión, el RNAi co-transcripcional resuelve los conflictos entre la transcripción y la replicación, asegurando la herencia adecuada de la heterocromatina.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La epigenética es la epigenética.
Sus antecedentes:
- La heterocromatina, el ADN compactado en los cromosomas eucariotas, es esencial para la estabilidad del genoma.
- Su herencia a través de la división celular se basa en la interferencia del ARN (RNAi) para guiar las modificaciones de la histona durante la replicación del ADN.
Objetivo del estudio:
- Para investigar la interacción entre la transcripción y la replicación del ADN en la heterocromatina pericentromérica en Schizosaccharomyces pombe.
- Para aclarar el papel de la interferencia del ARN co-transcripcional en la resolución de conflictos y asegurar la herencia de la heterocromatina.
Principales métodos:
- Estudió la disposición de los orígenes de replicación y el ARN no codificante en la heterocromatina pericentromérica.
- Se observaron los efectos de la interferencia de ARN (RNAi) en la liberación de ARN polimerasa II (Pol II) y la progresión de la replicación del ADN.
- Se analizaron los mecanismos de reparación de la bifurcación estancada en ausencia de ARNi.
Principales resultados:
- Una disposición alterna de los orígenes de replicación y el ARN no codificante en la heterocromatina pericentromérica crea competencia entre la transcripción y la replicación.
- El RNAi de co-transcripción facilita la liberación de la ARN polimerasa II (Pol II), lo que permite la replicación del ADN por la polimerasa de cadena principal.
- Las enzimas modificadoras de histonas asociadas con el tenedor de replicación propagan la heterocromatina.
- Sin RNAi, las horquillas de replicación estancadas se reparan a través de la recombinación homóloga, evitando la modificación de la histona.
Conclusiones:
- El RNAi de co-transcripción es un mecanismo clave que resuelve los conflictos de transcripción-replicación en la heterocromatina.
- Este proceso es vital para la herencia precisa de la heterocromatina a través de la mitosis.
- La interrupción del ARNi conduce a vías alternativas de reparación que no mantienen la estructura de la heterocromatina.
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