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Un interruptor de ARNm retroviral dependiente del equilibrio regula la recodificación traslacional
Brian Houck-Loomis1, Michael A Durney, Carolina Salguero
1Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.
Nature
|November 29, 2011
Resumen
Los retrovirus controlan con precisión los niveles de proteínas mediante la recodificación del ARN. Un interruptor dependiente de la protonación en el ARN del virus de la leucemia murina regula este proceso, manteniendo una proporción crítica de proteína Gag a Gag-Pol.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Virología Virología.
- Biología Estructural Biología estructural.
Sus antecedentes:
- Los retrovirus requieren proporciones precisas de proteínas Gag y Gag-Pol para su ensamblaje.
- La recodificación traslacional a través del frameshifting ribosómico o la lectura stop codon logra esta relación.
- El mecanismo que controla la frecuencia de recodificación sigue siendo elusivo.
Objetivo del estudio:
- Para dilucidar el mecanismo detrás de la recodificación traslacional retroviral.
- Para determinar cómo los motivos de ARN cis regulan las proporciones de proteínas Gag a Gag-Pol.
- Para investigar las bases estructurales de la recodificación del virus de la leucemia murina.
Principales métodos:
- Espectroscopia de Resonancia Magnética Nuclear (RMN) para determinar la estructura del ARN.
- Análisis de los interruptores conformacionales dependientes de la protonación.
- Correlación de la conformación del ARN con los niveles de expresión de proteínas in vivo.
Principales resultados:
- Se resolvió la estructura de RMN de la señal de recodificación del virus de la leucemia murina.
- Un interruptor dependiente de la protonación induce una conformación permisiva activa y de lectura.
- Esta conformación activa está poblada en ~6% a pH fisiológico, coincidiendo con las proporciones de proteínas in vivo.
- El ARN utiliza el acoplamiento quimiomecánico para un control preciso de la frecuencia de lectura.
Conclusiones:
- Un nuevo mecanismo basado en el equilibrio rige la recodificación traslacional en los retrovirus.
- Los cambios conformacionales del ARN dependientes de la protonación son clave para mantener las relaciones Gag/Gag-Pol.
- Este mecanismo puede ser ampliamente aplicable a otros eventos de recodificación traslacional, incluido el cambio de marco.
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