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Los ARN de transferencia (ARNt) actúan como acompañantes de ensamblaje durante la infección por poxvirus, facilitando la formación del complejo de ARN polimerasa viral. Esta nueva función implica el secuestro y reclutamiento de factores de transcripción viral específicos y no modificados de tRNAGln/Arg.

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Área de la Ciencia:

  • Biología molecular
  • Virología
  • Biología estructural

Sus antecedentes:

  • Los ARN de transferencia (ARNt) son conocidos principalmente por su papel esencial en la traducción de proteínas.
  • Los poxvirus, como el virus Mpox, codifican su propia ARN polimerasa (vRNAP) para la replicación.
  • Los mecanismos precisos de ensamblaje de los complejos macromoleculares virales no se comprenden completamente.

Objetivo del estudio:

  • Investigar una nueva función de los tRNA más allá de la traducción.
  • Para aclarar el papel de los tRNA específicos en el ensamblaje de la poxviral RNA polimerasa (vRNAP).
  • Comprender los mecanismos estructurales por los cuales los tRNA regulan la formación del complejo de transcripción viral.

Principales métodos:

  • Microscopía criolectrónica (Cryo-EM) para visualizar los productos intermedios de ensamblaje.
  • Ensayos bioquímicos para estudiar el secuestro de ARNt y el reclutamiento de factores.
  • Análisis de la estructura y los patrones de modificación del ARNt.

Principales resultados:

  • El tRNAGln/Arg identificado carece de modificaciones específicas como un acompañante de ensamblaje para el vRNAP poxviral.
  • Se demostró que este tRNA modificado orquesta el reclutamiento de factores de procesamiento de transcripción y ARNm.
  • Se reveló un mecanismo de ajuste inducido que involucra la internalización de la base anticodón G36, formando una estructura de ARNt no canónica.
  • Se ha demostrado que este mecanismo controla la transición al complejo de preiniciación.

Conclusiones:

  • Los ARN de transferencia (ARNt) poseen una función no reconocida anteriormente como acompañantes de ensamblaje en la replicación viral.
  • El secuestro específico y la adaptación estructural del tRNAGln/Arg son críticos para el ensamblaje y la función del vRNAP poxviral.
  • Este mecanismo de ensamblaje mediado por tRNA se conserva en el virus Mpox patógeno, destacando su importancia biológica.