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A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
09:04

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Published on: March 15, 2016

Un interruptor de ARN sensible al estrés regula la expresión de VEGFA.

Partho Sarothi Ray1, Jie Jia, Peng Yao

  • 1Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.

Nature
|December 23, 2008
PubMed
Resumen
Este resumen es generado por máquina.

Los investigadores descubrieron un nuevo interruptor de ARN en el ARNm del factor de crecimiento endotelial vascular humano-A (VEGFA). Este interruptor integra las señales de interferón gamma e hipoxia para controlar la traducción de VEGFA en las células mieloides.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Regulación genética Reglamento genético.
  • ARN Biología Biología ARN

Sus antecedentes:

  • Las regiones de ARN no codificantes regulan la expresión génica a través de la unión de ligandos.
  • Los riboswitches y otros switches de ARN responden a los metabolitos o a los metabolitos unidos a las proteínas.
  • Estos sistemas se encuentran en bacterias, hongos y plantas.

Objetivo del estudio:

  • Identificar y caracterizar un nuevo interruptor de ARN en el factor de crecimiento endotelial vascular humano-A (VEGFA) mRNA.
  • Para investigar cómo este interruptor integra las señales ambientales para modular la expresión génica.
  • Comprender el mecanismo de la regulación de la traducción VEGFA en las células mieloides.

Principales métodos:

  • Análisis de la región no traducida 3' (UTR) del ARNm VEGFA.
  • Investigación de la unión de proteínas a la VEGFA 3' UTR en respuesta a estímulos.
  • Caracterización de los cambios conformacionales en el interruptor de ARN.

Principales resultados:

  • Se identificó un interruptor de ARN independiente del metabolito en el ARNm VEGFA humano 3' UTR.
  • Este interruptor integra las señales del interferón (IFN) -gamma y la hipoxia.
  • El cambio conformacional del interruptor está regulado por la unión mutuamente exclusiva del inhibidor activado por IFN-gamma del complejo de traducción y la ribonucleoproteína nuclear heterogénea L (HNRNPL).

Conclusiones:

  • El VEGFA mRNA 3' UTR actúa como un nuevo interruptor de ARN, regulando la traducción de VEGFA en las células mieloides.
  • Este interruptor es dependiente de proteínas e integra múltiples señales ambientales.
  • Puede representar una nueva clase de interruptores de ARN desarrollados para la regulación génica en animales multicelulares.