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Regulación de todo el transcriptoma del empalme del pre-ARNm y la localización del ARNm por proteínas musculares
Eric T Wang1, Neal A L Cody, Sonali Jog
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Cell
|August 21, 2012
Resumen
Las proteínas de tipo Muscleblind (Mbnl) regulan el empalme de genes y la localización del ARNm. Comprender los objetivos de Mbnl proporciona nuevos conocimientos sobre la patogénesis de la distrofia miotónica (DM).
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- ARN Biología Biología ARN
Sus antecedentes:
- Las proteínas de tipo muscular ciego (Mbnl) son cruciales para el desarrollo muscular y ocular.
- Las proteínas Mbnl se agotan funcionalmente en la distrofia miotónica (DM) debido a las repeticiones expandidas de CUG/CCUG.
Objetivo del estudio:
- Para identificar objetivos funcionales y biofísicos de las proteínas Mbnl en todo el transcriptoma.
- Para aclarar el papel de las proteínas Mbnl en el procesamiento y la localización del ARN.
- Para explorar las implicaciones para la patogénesis de la distrofia miotónica (DM).
Principales métodos:
- Se emplearon la secuenciación de ARN (RNA-seq) y la secuenciación de CLIP (CLIP-seq).
- Se utilizó el mapeo de ARN de resolución de nucleótidos.
- Se realizó un análisis transcriptómico de los compartimentos subcelulares.
Principales resultados:
- Se identificaron varios cientos de eventos de empalme dependientes de Mbnl, lo que muestra la intercambiabilidad funcional entre Mbnl1 y Mbnl2.
- La unión de Mbnl cerca de los sitios de empalme se relacionó con la represión o activación del empalme de exones.
- Las Mbnls regulan globalmente la localización del ARNm, impactando la traducción y la secreción de proteínas.
Conclusiones:
- Las proteínas Mbnl tienen un papel global en la regulación del ARNm más allá del empalme, incluyendo la localización, la traducción y la secreción.
- Los hallazgos ofrecen nuevas perspectivas sobre los mecanismos moleculares subyacentes a la distrofia miotónica (DM).
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