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Los grupos de piRNA regulados en el desarrollo implican a MILI en el control del transposón.

Alexei A Aravin1, Ravi Sachidanandam, Angelique Girard

  • 1Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Howard Hughes Medical Institute (HHMI), 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.

Science (New York, N.Y.)
|April 21, 2007
PubMed
Resumen

Las proteínas PIWI de mamíferos, MIWI y MILI, suprimen las transposones a través de los piARN. Los mutantes de Mili muestran elementos LINE-1 desreprimidos y pérdida de metilación del ADN, lo que confirma las proteínas PIWI.

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Área de la Ciencia:

  • Genómica y Biología Molecular.
  • La epigenética y la regulación del transposón.

Sus antecedentes:

  • Aproximadamente el 50% de los genomas de mamíferos consisten en secuencias repetitivas, incluidas las transposones.
  • Se sabe que las proteínas Piwi controlan los transposones en Drosophila, pero su papel en los mamíferos no está claro debido a que los piRNA carecen de secuencias de repetición.

Objetivo del estudio:

  • Investigar el papel de las proteínas Piwi de los mamíferos (MIWI y MILI) en la supresión de los transposones.
  • Para identificar pequeños ARN que programan las proteínas Piwi para el control de los transposones en ratones.

Principales métodos:

  • Análisis bioinformático de pequeños ARN murinos para identificar los loci piRNA.
  • Caracterización de los loci de piRNA por similitudes con los elementos de control del transposón de Drosophila.
  • Análisis de ratones mutantes Mili para la desrepresión del transposón y los cambios en la metilación del ADN.

Principales resultados:

  • Descubrimiento de loci de piRNA regulados en el desarrollo en ratones, algunos que se asemejan a los loci de control maestro del transposón de Drosophila.
  • Evidencia de un bucle de amplificación adaptativa que involucra a MILI en la formación del extremo 5' del piRNA.
  • Los mutantes Mili exhiben desrepresión de los elementos de partículas LINE-1 e intracisternales A, con la pérdida asociada de la metilación del ADN L1.

Conclusiones:

  • Las proteínas PIWI de los mamíferos, particularmente MILI, juegan un papel crucial en la supresión de los transposones.
  • En los mamíferos existe un mecanismo evolucionariamente conservado de control del transposón mediado por PIWI.
  • Los hallazgos destacan la importancia de los piRNA y las proteínas PIWI en el mantenimiento de la estabilidad del genoma.