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2018, Número S1

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TIP Rev Esp Cienc Quim Biol 2018; 21 (S1)


Regulación de la traducción mediada por la proteína NSP3 de rotavirus

Contreras-Treviño HI, Padilla-Noriega L
Texto completo Cómo citar este artículo Artículos similares

Idioma: Español
Referencias bibliográficas: 49
Paginas: 124-133
Archivo PDF: 775.76 Kb.


PALABRAS CLAVE

NSP3, intermediarios de dimerización, proteostasis, inhibición traduccional.

RESUMEN

El estudio de los mecanismos utilizados por diversos virus para controlar la traducción de la célula hospedera y favorecer la expresión de proteínas virales ha sido muy instructivo para conocer mecanismos celulares fundamentales que regulan la traducción. La proteína NSP3 de los rotavirus de la especie A (RVA) es capaz de inhibir la traducción de los RNAm celulares como consecuencia de su unión al factor de iniciación de la traducción eIF4G y de estimular la traducción de los RNAm virales como consecuencia de su unión a la secuencia UGACC de su extremo 3’. Se ha propuesto que NSP3 inhibe la traducción por interferir con la circularización de los extremos 5’-3’ de los RNAm celulares mediada por eIF4E-eIF4G-PABP (proteína de unión a poli-A), y simultáneamente se propone que NSP3 estimula la traducción de los RNAm del RVA circularizándolos de manera análoga a la que realiza PABP en los RNAm celulares. Sin embargo, la importancia de la dimerización de NSP3 asistida por la chaperona HSP90 en su función inhibitoria de la traducción celular se desconoce. Recientemente, se exploró la importancia de los intermediarios de la dimerización de NSP3 sobre su función inhibitoria de la traducción, y se encontró que mutaciones puntuales en la región coiled-coil afectan la formación de los dímeros y conservan parcialmente su función inhibitoria de la traducción celular. Además, se detectó que los dímeros de NSP3 se degradan con mayor rapidez que los intermediarios de la dimerización. Estos datos demuestran que la función de NSP3 se adquiere previamente a la aparición de los dímeros, y sugiere que la susceptibilidad al proteasoma de las distintas formas oligoméricas de NSP3 son relevantes en el establecimiento de la función inhibitoria de la traducción celular.


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