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Identificación de genes de pequeñas vías de ARN utilizando patrones de conservación y divergencia filogenética
Yuval Tabach1, Allison C Billi, Gabriel D Hayes
1Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Nature
|February 1, 2013
Resumen
Los investigadores identificaron nuevas proteínas cruciales para las vías de interferencia de ARN (RNAi) y microARN (miRNA) mediante el análisis de los genomas eucariotas. Muchos cofactores de vías de ARN pequeños recién descubiertos están vinculados al empalme de ARN, lo que sugiere una conexión profunda entre estos procesos.
Área de la Ciencia:
- Genómica y Biología Molecular.
- Bioinformática y Biología Computacional.
- Regulación del gen de los eucariotas.
Sus antecedentes:
- Las vías de interferencia de ARN (RNAi) y microARN (miRNA) utilizan cofactores esenciales como Argonaute y Dicer para el procesamiento de ARN pequeño y el reconocimiento de objetivos.
- Estos pequeños cofactores de la vía del ARN exhiben diversos patrones de conservación evolutiva en los eucariotas, lo que refleja su importancia funcional.
Objetivo del estudio:
- Identificar nuevas proteínas involucradas en pequeñas vías de ARN mediante la comparación de perfiles filogenéticos a través de 86 genomas eucariotas divergentes.
- Integrar datos filogenéticos con información transcripcional y proteómica para predecir proteínas candidatas de la vía del ARN pequeño.
Principales métodos:
- Análisis comparativo de genómica de 86 genomas eucariotas para identificar proteínas con perfiles filogenéticos similares a los conocidos pequeños cofactores de ARN.
- Integración del análisis del perfil filogenético con la inferencia bayesiana, la corregulación transcripcional y los datos de interacción del proteoma.
- Validación funcional de proteínas candidatas de alta confianza a través de ensayos de silenciamiento de RNAi en organismos modelo.
Principales resultados:
- Identificación de un gran conjunto de cofactores candidatos de la vía del ARN pequeño, muchos exhibiendo perfiles filogenéticos similares a las proteínas conocidas.
- El cribado funcional confirmó que aproximadamente la mitad de los pequeños cofactores de ARN predichos son esenciales para el silenciamiento de RNAi.
- Muchas proteínas recientemente identificadas son ortológicas a los factores de empalme de ARN, lo que indica un vínculo entre el empalme y las vías de ARN pequeño.
Conclusiones:
- El estudio identificó con éxito numerosas proteínas nuevas involucradas en pequeñas vías de ARN, ampliando nuestra comprensión de los mecanismos de silenciamiento de genes.
- Existe una conexión significativa entre la maquinaria de empalme de ARN y el silenciamiento de genes mediado por ARN pequeño, respaldado por la correlación entre las proteínas argonautas, los componentes de ARN pequeño y la presencia de intrones en todas las especies.
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