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Formación libre de células de gránulos de ARN: dominios de secuencias de baja complejidad forman fibras dinámicas
Masato Kato1, Tina W Han, Shanhai Xie
1Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390-9152, USA.
Cell
|May 15, 2012
Resumen
Las secuencias de baja complejidad en las proteínas de unión al ARN impulsan la formación de fibras dinámicas similares a las amiloides. Estas fibras son componentes esenciales de los gránulos de ARN y pueden autoensamblarse en hidrogeles.
Área de la Ciencia:
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
Sus antecedentes:
- Las células eucariotas cuentan con gránulos de ARN, que son ensamblajes de proteínas y ARN.
- Las proteínas dentro de los gránulos de ARN a menudo poseen dominios de unión de ARN (por ejemplo, KH, RRM) y secuencias de baja complejidad (LC) de función incierta.
Objetivo del estudio:
- Para investigar la función de las secuencias de baja complejidad (LC) en las proteínas de unión al ARN.
- Comprender el papel de las secuencias de LC en la formación de gránulos de ARN y otras estructuras celulares no unidas a la membrana.
Principales métodos:
- Precipitación química utilizando un isoxazol biotinulado (b-isox) para identificar las proteínas que interactúan.
- Estudios in vitro sobre las propiedades de autoensamblaje de las secuencias LC.
- Difracción de rayos X y microscopía electrónica (EM) para analizar la estructura de los polímeros formados.
Principales resultados:
- Una sonda química (b-isox) precipitó numerosas proteínas de unión al ARN, muchas de las cuales son componentes de los gránulos de ARN.
- Se identificaron secuencias de LC como necesarias y suficientes para esta agregación mediada por b-isox.
- Las secuencias de LC pueden experimentar transiciones de fase para formar hidrogeles, que polimerizan en fibras dinámicas similares a las amiloides.
- Estas fibras son distintas de los amiloides patógenos, exhiben propiedades dinámicas y se adaptan a la polimerización heterotípica.
Conclusiones:
- Las secuencias LC juegan un papel crítico en el ensamblaje de proteínas de unión al ARN y la formación de gránulos de ARN.
- Las secuencias de LC actúan como bloques de construcción fundamentales para estructuras celulares dinámicas y no ligadas a la membrana.
- Los hallazgos proporcionan un nuevo marco para comprender la función de las secuencias de LC y la organización de los compartimentos celulares.
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