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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
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La N6-metiladenosina marca los microARN primarios para su procesamiento
Claudio R Alarcón1, Hyeseung Lee1, Hani Goodarzi1
1Laboratory of Systems Cancer Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Nature
|March 25, 2015
Resumen
La metiltransferasa tipo 3 (METTL3) agrega una marca m(6)A a los pri-miARN, lo que permite el reconocimiento de DGCR8 y el procesamiento de microARN. Esta modificación es esencial para la biogénesis de miRNA y los niveles globales de miRNA.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- ARN Biología Biología ARN
- La epigenética es la epigenética.
Sus antecedentes:
- La biogénesis del microARN (miRNA) se inicia con el procesamiento del miRNA primario (pri-miRNA) por el complejo de microprocesadores (DGCR8/DROSHA).
- El mecanismo preciso del reconocimiento DGCR8 de pri-miRNAs sobre otras estructuras de ARN sigue sin estar claro.
Objetivo del estudio:
- Para aclarar el mecanismo por el cual DGCR8 reconoce y se une pri-miRNAs.
- Identificar los factores que regulan el paso inicial de la biogénesis del miRNA.
Principales métodos:
- Experimentos celulares que involucran el agotamiento de METTL3 y la ganancia de función.
- Análisis bioquímicos que incluyen reacciones de procesamiento in vitro.
- Análisis de los niveles de pri-miRNA y miRNA maduro.
Principales resultados:
- METTL3 metila los pri-miRNAs en el sitio N(6) -metiladenosina (m(6) A, marcando su unión a DGCR8.
- El agotamiento de METTL3 reduce la interacción DGCR8-pri-miRNA, lo que lleva a una disminución del miRNA maduro y un aumento de los niveles de pri-miRNA.
- Los estudios in vitro confirman m(6) Una suficiencia para el procesamiento de pri-miRNA; METTL3 mejora la maduración del miRNA a nivel mundial.
Conclusiones:
- La modificación m(6)A, mediada por METTL3, es un regulador post-transcripcional crítico que promueve el reconocimiento y procesamiento de pri-miRNA por DGCR8.
- Este hallazgo revela un nuevo mecanismo que controla el inicio de la biogénesis del miRNA.
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