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Los factores de control de la calidad del ARN nuclean Clr4/SUV39H y desencadenan el ensamblaje constitutivo de la

Jasbeer S Khanduja¹, Richard I Joh¹, Monica M Perez¹

¹Massachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.

|May 30, 2024

Resumen

Los ARN largos no codificantes (ARNlnc) y los factores de control de calidad del ARN inician la formación de heterocromatina. Este proceso, independiente de los ARN pequeños, establece un estado basal amplificado por la interferencia de ARN para un silenciamiento epigenético robusto.

Área de la Ciencia:

Epigenética y regulación genética
Biología molecular
Biología de la cromatina

Sus antecedentes:

La formación de heterocromatina eucariota se basa en la trimetilación de la histona H3 lisina 9 (H3K9me), mediada principalmente por las proteínas de la familia Suv39.
Los modelos actuales en levadura de fisión sugieren que los ARN pequeños asociados a Argonaute1 (ARNs) nuclean Clr4/SUV39H en los centrómeros para H3K9me.
Los mecanismos precisos de nucleación de las proteínas Suv39 en la heterocromatina siguen siendo incompletamente entendidos.

Objetivo del estudio:

Investigar los mecanismos de nucleación de la H3K9 metiltransferasa Clr4/SUV39H en ausencia de ARNs y H3K9me.
Aclarar el papel de los ARN largos no codificantes (ARNlnc) y los factores de control de calidad del ARN en el inicio de la formación de heterocromatina.
Comprender la interacción entre la desacetilación y la metilación en la propagación de H3K9me.

Principales métodos:

Análisis genético en levadura de fisión para estudiar la formación de heterocromatina en condiciones de deficiencia de sRNA y H3K9me.
Ensayos bioquímicos para investigar la interacción del complejo MTREC/PAXT con los lncRNA y el Clr4/SUV39H.
Análisis de las modificaciones histónicas (H3K9me y acetilación de H3K9) para rastrear el establecimiento y la propagación de la heterocromatina.

Principales resultados:

El núcleo Mtl1 y Red1 (MTREC) / complejo PAXT nuclea Clr4 / SUV39H en un lncRNA heterocromático de una manera independiente del sRNA.
Sir2 y Clr3 se acumulan en el sitio de nucleación de lncRNA a través de mecanismos distintos.
Los ciclos iterativos de desacetilación y metilación de H3K9 facilitan la propagación de Clr4/SUV39H, estableciendo un estado basal de H3K9me.
El mecanismo de interferencia de ARN (RNAi) amplifica la señal H3K9me en los centrómeros, aumentando el establecimiento de la heterocromatina.

Conclusiones:

Los lncRNA y los factores de control de calidad del ARN sirven como centros de nucleación críticos para la heterocromatina.
Una vía independiente de sRNA que involucra lncRNAs establece un nivel básico de H3K9me.
Este estudio revela un nuevo mecanismo para el silenciamiento epigenético, destacando el doble papel de los lncRNA y el control de calidad del ARN en la formación de la heterocromatina.

Palabras clave:

Cloruro de hidrógeno Cloruro de sodio y sus derivados Desacetilación y metilación de H3K9 MTREC y NURS Se trata de un Señor 2 Formación de la heterocromatina de nuevo Núcleo de la heterocromatina ARN largos no codificantes el exosoma nuclear

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