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El ARN antisenso largo no codificante controla la traducción de Uchl1 a través de una repetición SINEB2 incorporada.

Claudia Carrieri1, Laura Cimatti, Marta Biagioli

  • 1Area of Neuroscience, International School for Advanced Studies (SISSA), via Bonomea 265, 34136 Trieste, Italy.

Nature
|October 16, 2012
PubMed
Resumen

Los investigadores descubrieron un nuevo tipo de ARN largo no codificante (ARNlnc) que regula la expresión génica. Este antisense Uchl1 lncRNA mejora la síntesis de proteínas, revelando una nueva capa de control genético post-transcripcional.

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Área de la Ciencia:

  • La genómica es la genómica.
  • Biología Molecular Biología Molecular
  • La neurociencia es la neurociencia.

Sus antecedentes:

  • La mayor parte del genoma de los mamíferos se transcribe, produciendo diversas moléculas de ARN, incluidos los ARN largos no codificantes (ARNlnc).
  • Los ncRNAs enriquecidos nuclearmente a menudo tienen funciones desconocidas, aunque algunos lncRNAs antisense regulan la expresión génica a través del emparejamiento sentido-antisense.
  • La ubiquitina carboxiterminal hidrolasa L1 (Uchl1) es crucial para la función cerebral y está implicada en enfermedades neurodegenerativas.

Objetivo del estudio:

  • Para identificar y caracterizar nuevos lncRNAs enriquecidos con nucleos.
  • Para investigar la función de un antisense de lncRNA recién identificado para el gen Uchl1.
  • Para aclarar los mecanismos reguladores de la síntesis de proteínas Uchl1.

Principales métodos:

  • Identificación de lncRNAs enriquecidos con núcleo utilizando análisis transcriptómico.
  • Validación experimental de la interacción del ARN Uchl1 antisense con el ARNm Uchl1.
  • Evaluación de los niveles de proteína Uchl1 bajo diversas condiciones, incluyendo la inhibición de mTORC1.
  • Análisis de la localización del ARN y la asociación del polisoma.

Principales resultados:

  • Se identificó un nuevo lncRNA enriquecido nuclearmente, el antisense Uchl1.
  • Antisense Uchl1 mejora la síntesis de proteínas Uchl1 después de la transcripción.
  • Su actividad se basa en una secuencia de superposición de 5' y un elemento SINEB2 incrustado.
  • La inhibición de mTORC1 inducida por la rapamicina aumenta la proteína UCHL1 al promover la exportación antisense de Uchl1 al citoplasma, lo que facilita la traducción.

Conclusiones:

  • Se ha identificado una nueva clase de lncRNA funcionales, el antisense Uchl1.
  • Antisense Uchl1 regula la síntesis de la proteína Uchl1 en el nivel post-transcripcional.
  • Las vías de señalización del estrés modulan la actividad de Uchl1 antisense, impactando la traducción de UCHL1 y revelando un nuevo mecanismo de control de la expresión génica.