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ARNl RMRP humano interactúa con helicasas de la familia DEAD y modula la función mitocondrial

Higor Sette Pereira1, Jason Luddu1, Govardhan Reddy Veerareddygari1

  • 1Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.

Proceedings of the National Academy of Sciences of the United States of America
|February 20, 2026
PubMed
Resumen

El ARN largo no codificante RMRP muestra flexibilidad estructural y regula la salud mitocondrial interactuando con helicasas de ARN. Este ARNl

Palabras clave:
helicasas DEAD-boxRMRPARN largo no codificantefunción mitocondrial

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Área de la Ciencia:

  • Biología Molecular
  • Genética
  • Bioquímica

Sus antecedentes:

  • El ARN largo no codificante (lncRNA) humano RMRP está implicado en enfermedades, pero su estructura y funciones no están claras.
  • El papel de RMRP, componente del complejo RNasa MRP, más allá de este complejo necesita ser dilucidado.

Objetivo del estudio:

  • Analizar exhaustivamente la estructura, las interacciones proteicas y las funciones mitocondriales de RMRP.
  • Comprender los mecanismos moleculares de RMRP en el mantenimiento de la función mitocondrial.

Principales métodos:

  • Dispersión de rayos X de ángulo pequeño (SAXS) para determinar la estructura de RMRP.
  • Estudios de interacción proteína-ARN con helicasas de ARN DEAD-box DDX5 y DDX3X.
  • Análisis de la función mitocondrial y la expresión génica tras cambios en los niveles de RMRP.

Principales resultados:

  • RMRP exhibe cambios estructurales dependientes de Mg2+, adoptando diferentes conformaciones.
  • Las helicasas DDX5 y DDX3X interactúan con RMRP, influyendo en su localización y actividad.
  • La reducción de los niveles de RMRP perjudica la estabilidad mitocondrial, causando despolarización y aumento de ROS.
  • RMRP regula las proteínas mitocondriales codificadas nuclearmente DNAJC11 y NDUFS8.

Conclusiones:

  • RMRP es un ARNl estructuralmente dinámico crucial para la integridad mitocondrial.
  • RMRP colabora con helicasas de ARN para mantener la salud mitocondrial a través de la regulación génica específica.
  • Los hallazgos ofrecen información sobre los trastornos relacionados con RMRP y las posibles estrategias terapéuticas.