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Los componentes de interferencia de ARN asociados a la cromatina contribuyen a la regulación de la transcripción en
Filippo M Cernilogar1, Maria Cristina Onorati, Greg O Kothe
1Dulbecco Telethon Institute, Epigenetics and Genome Reprogramming, IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Nature
|November 8, 2011
Resumen
Las proteínas clave de interferencia de ARN (RNAi), Dicer 2 (DCR2) y Argonaute 2 (AGO2), se asocian con genes activos e influyen en la dinámica de la ARN polimerasa II, revelando un papel en la regulación de la transcripción en animales.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La epigenética es la epigenética.
Sus antecedentes:
- Las vías de interferencia de ARN (RNAi) regulan principalmente la expresión génica post-transcripcionalmente en el citoplasma.
- Se conocen las funciones nucleares de los componentes de ARNi en la regulación epigenética y la formación de heterocromatina.
- Los mecanismos de silenciamiento de genes transcripcionales mediados por ARNi y la dinámica de la cromatina en animales siguen siendo en gran medida poco claros.
Objetivo del estudio:
- Para investigar la función nuclear de los componentes clave del ARNi, Dicer 2 (DCR2) y Argonaute 2 (AGO2), en la dinámica de la cromatina y la regulación de la transcripción en animales multicelulares.
- Aclarar el papel de DCR2 y AGO2 en el control de la actividad y posicionamiento de la ARN polimerasa II.
Principales métodos:
- Estudios de asociación de cromatina de DCR2 y AGO2.
- Análisis de los defectos de transcripción en las mutaciones de pérdida de función DCR2 y AGO2.
- Evaluación de la dinámica de la ARN polimerasa II después del choque térmico en fondos mutantes DCR2 y AGO2.
- Secuenciación profunda de ARN pequeño asociado a AGO2 (AGO2 RIP-seq).
Principales resultados:
- DCR2 y AGO2 se asocian con la cromatina, en particular con los loci eucromáticos transcripcionalmente activos.
- La pérdida de la función DCR2 o AGO2 perturba el posicionamiento de la ARN polimerasa II en los promotores.
- Las mutaciones en DCR2 y AGO2 perjudican la dinámica global de la ARN polimerasa II, especialmente después de un choque térmico.
- AGO2 está enriquecido con pequeños ARN que se asignan al loci promotor y genético, con un sesgo para la hebra antisentido después del choque térmico.
Conclusiones:
- DCR2 y AGO2 están asociados globalmente con los loci activos de transcripción en las células animales.
- Estos componentes de ARNi juegan un papel importante en el silenciamiento de genes transcripcionales y la dinámica de la cromatina.
- DCR2 y AGO2 pueden controlar la procesividad de la ARN polimerasa II, dando así forma al transcriptoma.
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