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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
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ARN largos no codificantes con función de potenciador en las células humanas.

Ulf Andersson Ørom1, Thomas Derrien, Malte Beringer

  • 1The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.

Cell
|October 5, 2010
PubMed
Resumen
Este resumen es generado por máquina.

Los ARN largos no codificantes (ARNnc) activan sorprendentemente la expresión génica, desafiando la comprensión previa de su función. Este estudio revela su papel en la regulación de los genes críticos del desarrollo.

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Área de la Ciencia:

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

Sus antecedentes:

  • Los ARN largos no codificantes (ARNnc) representan una porción significativa del transcriptoma de los mamíferos, sin embargo, sus funciones siguen siendo en gran medida desconocidas.
  • La investigación existente enlaza principalmente los ncRNA con los mecanismos de silenciamiento genético como la inactivación de X y la impresión.

Objetivo del estudio:

  • Para caracterizar los ncRNA largos utilizando la anotación del genoma humano GENCODE.
  • Investigar el papel funcional de los ncRNA largos en la regulación de la expresión génica.

Principales métodos:

  • Utilizó la anotación GENCODE para identificar más de mil long ncRNAs expresados a través de múltiples líneas celulares humanas.
  • Realizó experimentos de agotamiento genético para evaluar el impacto en la expresión génica codificante de proteínas vecinas.
  • Se emplearon ensayos de transcripción heterólogos para confirmar el papel de los ncRNA en la activación génica.

Principales resultados:

  • Se identificó una inesperada función similar a un potenciador para un subconjunto de long ncRNAs en líneas celulares humanas.
  • El agotamiento de los ncRNA específicos dio lugar a una expresión reducida de los genes codificadores de proteínas cercanos, incluidos los reguladores clave del desarrollo como SCL (TAL1), Snai1 y Snai2.
  • Demostró la necesidad de estos ncRNA para activar la expresión génica.

Conclusiones:

  • Revela un nuevo papel para los ARN largos no codificantes como activadores de la expresión génica.
  • Destaca la participación de los ncRNA en la regulación de genes críticos esenciales para el desarrollo y la diferenciación.
  • Desafía la visión predominante de los ncRNAs únicamente como silenciadores de genes.