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qiRNA es un nuevo tipo de ARN pequeño interferente inducido por daño al ADN
Heng-Chi Lee1, Shwu-Shin Chang, Swati Choudhary
1Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Nature
|May 16, 2009
Resumen
El daño en el ADN desencadena la creación de nuevos ARN pequeños llamados qiRNA en Neurospora crassa, que interactúan con QDE-2. Estos qiRNAs son cruciales para la respuesta al daño del ADN, potencialmente inhibiendo la traducción de proteínas.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- ARN Biología Biología ARN
Sus antecedentes:
- Las vías de interferencia de ARN (RNAi) utilizan ARN pequeños para el silenciamiento de genes en eucariotas.
- Más allá de los siARN y los miARN, otros ARN pequeños regulan los genes, las células germinales y los transposones.
- Los ARN aberrantes (aARN) son precursores de algunos ARN pequeños, pero su síntesis y reconocimiento son poco conocidos.
Objetivo del estudio:
- Para investigar el mecanismo de la síntesis de ARN pequeño y el reconocimiento en respuesta al daño del ADN.
- Identificar nuevos ARN pequeños y sus funciones en eucariotas, específicamente en Neurospora crassa.
- Para aclarar la función de la proteína argonauta QDE-2 y sus pequeños ARN asociados.
Principales métodos:
- Inducción del daño del ADN en Neurospora crassa.
- Análisis de pequeñas poblaciones de ARN utilizando secuenciación.
- Identificación y caracterización de nuevos ARN pequeños (ARNs qi) y sus precursores (ARNs a).
- Análisis genético de mutantes de la vía del ARNi (QDE-1, QDE-3) y su respuesta al daño del ADN.
Principales resultados:
- El daño en el ADN induce la expresión de QDE-2 y una nueva clase de ARN pequeños de 20-21 nucleótidos, denominados qiRNAs.
- La producción de qiRNA requiere ARN dependiente de ARN, ARN polimerasa QDE-1, helicasa QDE-3 y otras.
- La biogénesis de qiRNA depende de los aRNA inducidos por daño en el ADN, sintetizados por una polimerasa de ARN dependiente del ADN (probablemente QDE-1).
- Los mutantes de Neurospora RNAi exhiben una mayor sensibilidad al daño del ADN.
Conclusiones:
- Una nueva vía para la biogénesis de ARN pequeño (qiRNA) se activa por el daño del ADN en Neurospora crassa.
- qiRNAs, que se originan en el ADN ribosomal, se procesan a partir de aRNAs inducidos por el daño del ADN.
- La maquinaria de RNAi, incluyendo QDE-1 y QDE-3, está involucrada en la producción de qiRNA y la respuesta al daño del ADN.
- qiRNAs pueden desempeñar un papel en la respuesta al daño del ADN mediante la modulación de la traducción de proteínas.
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