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Dinámica evolutiva de la regulación de genes y isoformas en tejidos de mamíferos
Jason Merkin1, Caitlin Russell, Ping Chen
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|December 22, 2012
Resumen
La mayoría de la expresión génica de los mamíferos se conserva a través de los tejidos, pero los patrones alternativos de empalme varían significativamente según el linaje. Los investigadores identificaron nuevos elementos de empalme y factores reguladores clave, revelando conocimientos sobre la evolución de la regulación génica.
Área de la Ciencia:
- La genómica comparada es una genómica comparada.
- Biología molecular La biología molecular.
- Biología evolutiva Biología evolutiva.
Sus antecedentes:
- El empalme alternativo genera diversos ARN mensajeros (ARNm) de los genes de los mamíferos.
- La conservación del empalme alternativo a través de tejidos y especies de mamíferos sigue siendo en gran medida no caracterizada.
Objetivo del estudio:
- Investigar la conservación del empalme alternativo específico del tejido a través de linajes de mamíferos.
- Para identificar nuevos exones empalmados alternativamente y elementos reguladores de empalme conservados.
Principales métodos:
- Secuenciación profunda de ADN complementario (ADNc) de nueve tejidos de cuatro especies de mamíferos y una ave.
- Análisis bioinformático para identificar eventos de empalme alternativos conservados y específicos del linaje.
- Análisis de motivos de secuencia asociados con exones alternativos conservados para inferir factores reguladores.
Principales resultados:
- Los programas de expresión génica específicos de los tejidos se conservan en gran medida en los mamíferos.
- El empalme alternativo se conserva en un subconjunto de tejidos, con patrones frecuentes específicos del linaje.
- Se descubrieron miles de nuevos exones alternativos específicos de linaje y conservados.
- Los exones alternativos conservados muestran firmas de unión de los factores de empalme MBNL, PTB, RBFOX, STAR y TIA.
- El empalme alternativo con frecuencia tiene un impacto en la fosforilabilidad de las proteínas, lo que potencialmente limita las vías de señalización de la quinasa.
Conclusiones:
- La regulación de empalme alternativo evolucionó de manera diferente a través de los linajes de mamíferos.
- Es probable que los factores de empalme como MBNL, PTB, RBFOX, STAR y TIA sean antiguos reguladores del empalme alternativo de los mamíferos.
- El empalme alternativo juega un papel importante en la modulación de la función de las proteínas y las redes de señalización celular.
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