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Mateusz Mendel¹, Kamila Delaney¹, Radha Raman Pandey¹

¹Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland.

|April 30, 2021

Resumen

La modificación del ARN de N6-metiladenosina (m6A) por METT-10 inhibe el empalme del pre-ARNm de la S-adenosilmetionina sintetasa en C. elegans. Este interruptor m6A desencadenado por la dieta regula la homeostasis de SAM y la inhibición del empalme se conserva en los mamíferos.

Área de la Ciencia:

Biología molecular
La epigenética
Biología del ARN

Sus antecedentes:

La N6-metiladenosina (m6A) es una modificación prevalente del ARN que influye en el destino del ARNm.
El escritor m6A METT-10 en C. elegans es un ortólogo del ratón METTL16.

Objetivo del estudio:

Investigar el papel de METT-10 en la regulación de la S-adenosilmetionina (SAM) sintetasa en el empalme del pre-ARNm.
Aclarar el mecanismo de inhibición del empalme mediado por m6A y su conservación.

Principales métodos:

Secuenciación y análisis de ARN
Pruebas de empalme
Análisis de la producción de proteínas
Ensayos bioquímicos para estudiar las interacciones proteína-ARN

Principales resultados:

METT-10 deposita m6A en el sitio de empalme 3' del pre-ARNm de la SAM sintetasa en C. elegans.
Esta modificación m6A inhibe el empalme y la producción de proteínas, actuando como un interruptor que responde a la dieta.
La inhibición del empalme por el sitio de empalme 3' m6A se conserva en los mamíferos, impidiendo la unión de U2AF35.

Conclusiones:

La modificación m6A en el sitio de empalme 3' es un mecanismo antiguo para regular el empalme.
Esta vía controla la expresión de la SAM sintetasa y la homeostasis en respuesta a las señales dietéticas.
Los hallazgos revelan un mecanismo conservado de control de empalme mediado por ARN con implicaciones para la regulación génica.

Palabras clave:

Sitio de empalme de 3'METT-10 (en inglés)METTL16 (en inglés)La homeostasis del SAM La SAM sintetasa U2AF35/65 y sus derivados U6 ARNn En el caso de los La espermatogénesis el empalme

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