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Una metilación de ARN regula el destino de los retrovirus endógenos

Tomasz Chelmicki¹, Emeline Roger², Aurélie Teissandier²

¹Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, Paris, France. tomasz.chelmicki@curie.fr.

|January 14, 2021

Resumen

La metilación del ARN de N-metiladenosina (m⁶A) restringe los retrovirus endógenos (ERV) al reducir la estabilidad de los ARNm ERV. Este proceso de modificación del ARN es crucial para mantener la integridad celular mediante la eliminación de especies de ARN retroviral potencialmente dañinas.

Área de la Ciencia:

Biología molecular
La genética
La epigenética

Sus antecedentes:

Los retrovirus endógenos (ERV) son secuencias retrovirales integradas que afectan la regulación del genoma y la fisiología celular.
La falta de represión de los ERV está relacionada con enfermedades como el cáncer, la infertilidad, la senescencia y la neurodegeneración.

Objetivo del estudio:

Identificar los mecanismos que restringen los retrovirus endógenos (ERV).
Investigar el papel de la metilación del ARN m6 en la regulación del ERV.

Principales métodos:

Pantalla de eliminación de CRISPR a escala genómica en células madre embrionarias de ratón.
Análisis de la abundancia de ARNm y los niveles de proteínas tras el agotamiento del complejo metiltransferasa (METTL3-METTL14).
Monitoreo del estado de la cromatina y la estabilidad del ARNm.

Principales resultados:

Una metilación de ARN restringe las ERV, específicamente dirigida a las partículas A intracisternas (IAP) y los elementos ERVK.
El agotamiento del complejo METTL3-METTL14 aumenta la abundancia de ARNm y proteínas de la PAI.
Una metilación reduce principalmente la vida media del ARNm IAP a través de las proteínas lectoras de YTHDF.

Conclusiones:

La metilación del ARN, específicamente m6A, actúa como un mecanismo de protección contra las especies reactivas de ARN derivadas del ERV.
Esta modificación del ARN es vital para mantener la integridad celular, particularmente cuando el silenciamiento de la transcripción es menos efectivo.

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