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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Un gran ARN no codificante intergenico inducido por p53 media la represión genética global en la respuesta p53
Maite Huarte1, Mitchell Guttman, David Feldser
1The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. mhuarte@broadinstitute.org
Cell
|August 3, 2010
Resumen
Los investigadores identificaron grandes ARN no codificantes intergenéticos (ARN linc) regulados por el p53. Un lincRNA, lincRNA-p21, actúa como un represor, interactuando con hnRNP-K para controlar la expresión génica y la apoptosis.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La genómica es la genómica.
- ARN Biología Biología ARN
Sus antecedentes:
- Se han identificado más de 1000 ARN no codificantes intergenicos grandes (ARN linc).
- Estas moléculas de ARN conservadas están implicadas en varios procesos biológicos.
Objetivo del estudio:
- Para identificar los lincRNA regulados por el supresor de tumores p53.
- Investigar la función de un nuevo lincRNA regulado por p53 en el control de la transcripción.
Principales métodos:
- Identificación de los lincRNAs regulados por p53.
- Análisis funcional del lincRNA-p21 utilizando perfiles de expresión génica.
- Investigación de las interacciones proteína-ARN utilizando la coinmunoprecipitación.
- Evaluación de la localización de hnRNP-K y su papel en la regulación génica.
Principales resultados:
- Identificación del lincRNA-p21 como un transcrito regulado por el p53.
- lincRNA-p21 actúa como un represor de la transcripción, afectando a cientos de genes objetivo.
- La represión mediada por el lincRNA-p21 requiere una asociación física con el hnRNP-K.
- Esta interacción es crucial para la localización de hnRNP-K y la apoptosis mediada por p53.
Conclusiones:
- p53 regula los lincRNAs, incluido el lincRNA-p21, que juega un papel represivo en las respuestas transcripcionales.
- lincRNA-p21 funciona asociándose con hnRNP-K, influyendo en su localización genómica y modulando la expresión génica.
- Se propone un modelo en el que los factores de transcripción activan los lincRNA que actúan como represores mediante el reclutamiento de complejos represivos para atacar genes.
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