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El CPEB1 coordina la formación alternativa de 3'-UTR con la regulación traslacional

Felice-Alessio Bava¹, Carolina Eliscovich, Pedro G Ferreira

¹Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.

|February 26, 2013

Resumen

La proteína de unión del elemento de poliadenilación citoplasmática 1 (CPEB1) controla el procesamiento de la región no traducida 3' (3' UTR) del ARN mensajero. Esta proteína de unión al ARN acorta las UTR 3', lo que afecta la traducción, la proliferación celular y el cáncer.

Área de la Ciencia:

Biología Molecular Biología Molecular
ARN Biología Biología ARN
Biología del cáncer Biología del cáncer.

Sus antecedentes:

Más de la mitad de los genes de los mamíferos producen ARN mensajero múltiple (ARNm) isoformas con diferentes regiones 3 'no traducidas (3' UTRs).
Estas 3' UTRs contienen secuencias reguladoras cruciales para procesos como la proliferación celular y a menudo están implicadas en el cáncer.
Los mecanismos que rigen el procesamiento alternativo de 3' UTR siguen siendo en gran medida indefinidos.

Objetivo del estudio:

Investigar el papel de la proteína 1 de unión al elemento de poliadenilación citoplasmática (CPEB1) en la regulación del procesamiento alternativo de 3' UTR.
Para aclarar cómo CPEB1 coordina la traducción de ARNm con el procesamiento 3' UTR.

Principales métodos:

Investigó la localización subcelular de CPEB1 (núcleo y citoplasma).
Se analizó la interacción de CPEB1 con los factores de empalme y los pre-ARNm.
Se evaluó el impacto de CPEB1 en la poliadenilación alternativa y el empalme alternativo.

Principales resultados:

CPEB1 se traslada al núcleo y co-localiza con los factores de empalme.
CPEB1 media el acortamiento de cientos de UTR 3' de ARNm, afectando la eficiencia de la traducción citoplasmática.
La unión de CPEB1 a los pre-ARNm influye en el uso alternativo del sitio de poliadenilación y el empalme alternativo al inhibir el reclutamiento de U2AF65.
El acortamiento de 3' UTR mediado por CPEB1 está correlacionado con el aumento de la proliferación celular y la tumorigénesis.

Conclusiones:

CPEB1 posee una función novedosa en el control del procesamiento alternativo 3' UTR.
CPEB1 integra el procesamiento 3' UTR con la regulación de la traducción del ARNm a través de sus actividades nucleares y citoplasmáticas duales.
El papel de CPEB1 en el procesamiento de 3' UTR tiene implicaciones para la comprensión de la proliferación celular y el desarrollo del cáncer.

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