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El complejo DBIRD integra el empalme alternativo de ARNm con el alargamiento de la transcripción de ARN polimerasa II
Pierre Close1, Philip East, A Barbara Dirac-Svejstrup
1Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
Nature
|March 27, 2012
Resumen
El nuevo complejo DBIRD enlaza la ARN polimerasa II (RNAPII) con las partículas de ribonucleoproteína mensajera (mRNP). Este complejo integra el alargamiento de transcripción con el empalme alternativo, particularmente para los exones en el ADN rico en (A + T).
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El empalme del ARN mensajero alternativo (ARNm) genera complejidad proteómica a partir de un conjunto genético limitado.
- El empalme está acoplado a la transcripción e influenciado por la tasa de alargamiento de la transcripción.
- La conexión entre la transcripción de ARN polimerasa II (RNAPII) y las partículas de ribonucleoproteína mensajera (mRNP) sigue sin estar clara.
Objetivo del estudio:
- Para caracterizar el interactoma humano de las partículas mRNP asociadas a la cromatina.
- Identificar los factores que vinculan el RNAPII, las partículas mRNP y la regulación del empalme.
- Para aclarar el papel de estos factores en la integración de la transcripción y el empalme.
Principales métodos:
- Análisis del interactoma humano de las partículas de mRNP asociadas a la cromatina.
- Identificación y caracterización de los complejos proteicos que interactúan con el RNAPII.
- Agotamiento mediado por la interferencia de ARN (RNAi) para evaluar el impacto funcional.
- Análisis de las tasas de alargamiento de transcripción y patrones alternativos de empalme.
Principales resultados:
- Se identificó el complejo DBIRD, que contiene DBC1 y ZNF326 (ZIRD), como un nuevo interactor RNAPII.
- DBIRD se une directamente al RNAPII y está localizado en los exones afectados.
- DBIRD regula el empalme alternativo de exones en el ADN rico en (A + T).
- El agotamiento de DBIRD causa disminuciones específicas de la región en el alargamiento de transcripción.
Conclusiones:
- El complejo DBIRD actúa en la interfaz de las partículas mRNP y RNAPII.
- DBIRD integra el alargamiento de transcripción con la regulación del empalme alternativo.
- Este mecanismo contribuye a la complejidad proteómica de los mamíferos.
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