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El silenciamiento epigenético dependiente del ARN dirige la regulación descendente de la transcripción causada por

Hannes Eimer¹, Sridevi Sureshkumar¹, Avilash Singh Yadav¹

¹School of Biological Sciences, Monash University, Clayton Campus, VIC 3800, Australia.

|July 31, 2018

Resumen

Las expansiones de repetición de tripletes desencadenan ARN interferentes cortos (siRNA) y cambios epigenéticos, lo que lleva al silenciamiento de genes. Este mecanismo, que involucra la metilación del ADN dependiente del ARN (RdDM), explica cómo estas expansiones causan fenotipos de enfermedades.

Área de la Ciencia:

La genética
La epigenética
Biología molecular

Sus antecedentes:

Las expansiones repetidas intrónicas están relacionadas con enfermedades como la ataxia de Friedreich.
La desregulación de la expresión génica acompaña a estas expansiones, pero los mecanismos siguen sin estar claros.

Objetivo del estudio:

Investigar los mecanismos moleculares subyacentes a la regulación descendente de la transcripción causada por las expansiones de repetición de tripletes intrónicos.
Aclarar el papel de las modificaciones epigenéticas y de los ARN pequeños en este proceso.

Principales métodos:

Análisis de una expansión intrónica del triplete GAA/TTC en el gen IIL1 de la Arabidopsis thaliana.
Investigar el papel de los componentes de la vía de metilación del ADN dependiente del ARN (RdDM) y el DICER LIKE-3.

Principales resultados:

La expansión repetida de tripletes en IIL1 condujo a una acumulación de siRNA de 24 nt y marcas de histona represiva.
La eliminación de los componentes de la vía DCL3 o RdDM suprimió la regulación a la baja de IIL1 y los fenotipos asociados.
La biogénesis del siRNA y el RdDM son críticos para el silenciamiento genético inducido por la expansión repetida.

Conclusiones:

Las expansiones de repetición de triplet pueden inducir la producción local de ARN pequeño interferente (siRNA).
Esta producción de siRNA media la regulación descendente de la transcripción a través de la metilación del ADN dependiente del ARN (RdDM).
Los hallazgos revelan un nuevo mecanismo epigenético que vincula las expansiones repetidas con el silenciamiento genético y la enfermedad.

Palabras clave:

Los ejemplares de Arabidopsis La ataxia de Friedreich Trayectoria de la RdDM El silenciamiento epigenético Los siRNAs Regulación descendente de la transcripción Triple expansión de repetición

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