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Un nuevo motivo de ARN basado en la estructura de bucles r(UUCG) inusualmente estables 2',5'-enlazados

Alexei Yu Denisov¹, Rami N Hannoush, Kalle Gehring

¹Department of Biochemistry and Montreal Joint Centre for Structural Biology, McGill University, Montreal, QC, H3G 1Y6, Canada.

Journal of the American Chemical Society

|September 18, 2003

Resumen

2 2 2 2 2 2 2 El hombre de la ciudad

Área de la Ciencia:

Biología Molecular Biología Molecular
La bioquímica es la bioquímica.
Biología Estructural Biología estructural.

Sus antecedentes:

Las horquillas de ARN nativo con bucles 3',5'-enlazados son termodinámicamente estables.
Los bucles de ARN 2',5'-enlazados muestran una estabilidad superior, independientemente de la composición del tallo.

Objetivo del estudio:

Determinar la estructura de la solución de las horquillas estables con bucles de ARN 2',5'-enlazado (UUCG).
Investigar la base estructural para la estabilidad mejorada de los bucles de 2',5'-ARN.

Principales métodos:

Espectroscopia de Resonancia Magnética Nuclear (RMN) para determinar la estructura de la solución.
Análisis del emparejamiento de bases, el apilamiento de bases y las interacciones azúcar-azúcar.

Principales resultados:

El bucle de ARN 2',5'-enlazado adopta un nuevo pliegue distinto de los bucles 3',5'-enlazados.
La estabilidad se atribuye al emparejamiento de bases oscilantes U5:G8, al apilamiento extensivo de bases y a los contactos azúcar-base/azúcar-azúcar.
El par de bases U5:G8 extiende el tallo, mientras que las pilas U6 en U5 y C7 están expuestas.

Conclusiones:

La estructura y la unión únicas de los ribonucleótidos 2',5'-enlazados explican la estabilidad mejorada de estos tetraloops.
Los bucles de 2',5'-ARN representan un nuevo motivo estructural con implicaciones para el diseño de terapias basadas en ARN.
Los hallazgos apoyan el uso de bucles de 2',5'-ARN en aptameros, ribozimas y agentes antisense.

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