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NRMT es una alfa-N-metiltransferasa que metila el RCC1 y la proteína del retinoblastoma
Christine E Schaner Tooley1, Janusz J Petkowski, Tara L Muratore-Schroeder
1Department of Microbiology, Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. ces5g@virginia.edu
Nature
|July 30, 2010
Resumen
Los científicos descubrieron la primera alfa-N-metiltransferasa, NRMT, crucial para la metilación de las proteínas. Este hallazgo explica cómo las proteínas como RCC1 son metiladas, impactando la división celular y la segregación cromosómica.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- La metilación post-traducional del grupo alfa-amino se observó hace más de 30 años en proteínas ribosomales bacterianas.
- La función y la enzimología de la alfa-N-metilación siguen siendo en gran medida desconocidas, siendo RCC1 la única proteína con función biológica identificada para esta modificación.
- Los mutantes RCC1 con defecto de metilación exhiben defectos de unión al ADN y anomalías mitóticas, lo que pone de relieve la necesidad de identificar la metiltransferasa responsable.
Objetivo del estudio:
- Para identificar la enzima responsable de la alfa-N-metilación de las proteínas.
- Para aclarar la función biológica y la importancia de la alfa-N-metilación en los procesos celulares.
- Para identificar nuevos sustratos y comprender el mecanismo de reconocimiento de la alfa-N-metiltransferasa.
Principales métodos:
- Descubrimiento y nombramiento de la N-terminal RCC1 metiltransferasa (NRMT).
- Acoplamiento de sustrato y análisis mutacional de RCC1 para definir la secuencia de reconocimiento de NRMT.
- Identificación de nuevos objetivos de metilación, incluidos el SET y la proteína del retinoblastoma (RB).
- Los experimentos de knockdown NRMT para observar los fenotipos celulares.
Principales resultados:
- Se identificó la primera alfa-N-metiltransferasa, la MTNR.
- Se definió la secuencia de reconocimiento de sustratos de NRMT, lo que condujo al descubrimiento de nuevos sustratos como SET y RB.
- La eliminación de NRMT imitaba los fenotipos de los mutantes RCC1 con defecto de metilación, incluida la formación de múltiples husos.
- La metilación alfa-N es crítica para la formación adecuada del huso bipolar y la segregación cromosómica.
Conclusiones:
- NRMT es la primera alfa-N-metiltransferasa identificada, responsable de la metilación de proteínas con un motivo N-terminal específico.
- La metilación alfa-N, mediada por NRMT, juega un papel vital en asegurar una segregación cromosómica precisa y la formación de husos bipolares.
- Este descubrimiento abre nuevas vías para comprender las implicaciones funcionales de la alfa-N-metilación en varios procesos biológicos.
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