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Highly Efficient Ligation of Small RNA Molecules for MicroRNA Quantitation by High-Throughput Sequencing
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Los círculos naturales de ARN funcionan como esponjas eficientes de microARN.

Thomas B Hansen1, Trine I Jensen, Bettina H Clausen

  • 1Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Alle 3, 8000C, Aarhus, Denmark.

Nature
|March 1, 2013
PubMed
Resumen

Los ARN circulares (circRNA) pueden actuar como esponjas de miRNA. Un nuevo circRNA, ciRS-7, funciona como una potente esponja para el microRNA-7 (miR-7), impactando la expresión génica en el cerebro.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Genética La genética.
  • ARN Biología Biología ARN

Sus antecedentes:

  • Los microARN (miRNA) regulan la expresión génica después de la transcripción.
  • La actividad de miRNA puede ser modulada por RNAs endógenos (ceRNAs) competidores y por el mimetismo de dianas.
  • Los ARN circulares (circRNA) son una clase de moléculas de ARN con potencial regulador.

Objetivo del estudio:

  • Para investigar la función de un circRNA altamente expresado en el cerebro humano y del ratón.
  • Para determinar si este circRNA actúa como una esponja de miRNA.
  • Para explorar las implicaciones de la esponjación de miRNA mediada por circRNA en vivo.

Principales métodos:

  • Identificación y caracterización de un nuevo circRNA (ciRS-7).
  • Evaluación de la interacción de ciRS-7 con las proteínas Argonaute (AGO) y miR-7.
  • Análisis del efecto de ciRS-7 en la actividad de miR-7 y la expresión génica diana.
  • Análisis in vivo de la coexpresión de ciRS-7 y miR-7 en el cerebro de ratón.
  • Investigación de otro circRNA (Sry) como una esponja de miRNA.

Principales resultados:

  • Se identificó un nuevo circRNA, ciRS-7, y se demostró que contiene numerosos sitios diana de miR-7.
  • ciRS-7 se asocia con las proteínas AGO de una manera dependiente de miR-7.
  • ciRS-7 funciona como una potente esponja miR-7, suprimiendo la actividad de miR-7 y aumentando los niveles objetivo de miR-7.
  • Se observó la expresión superpuesta de ciRS-7 y miR-7 en regiones específicas del cerebro de ratón.
  • Se demostró que el circRNA Sry actúa como una esponja miR-138, lo que indica un fenómeno general.

Conclusiones:

  • Los ARN circulares pueden funcionar como esponjas endógenas de miRNA.
  • ciRS-7 es una esponja funcional para miR-7, regulando su actividad en el cerebro.
  • La formación de CircRNA representa un mecanismo general para la regulación del miRNA y la regulación de los genes.