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El trans-splicing en C. elegans genera el regulador negativo de RNAi ERI-6/7

Sylvia E J Fischer¹, Maurice D Butler, Qi Pan

¹Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

|September 12, 2008

Resumen

Los investigadores identificaron mutaciones en los genes eri-6 y eri-7 en Caenorhabditis elegans, revelando un nuevo regulador de la vía RNAi. Esta proteína helicasa controla las vías de interferencia de ARN tanto exógenas como endógenas.

Área de la Ciencia:

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

Sus antecedentes:

La vía de interferencia de ARN (RNAi) utiliza ARN pequeños para regular la expresión génica.
Las mutaciones que afectan a los componentes del ARNi pueden revelar las interacciones de la vía y los mecanismos reguladores.

Objetivo del estudio:

Para identificar nuevos reguladores de las pequeñas vías de ARN en Caenorhabditis elegans.
Para investigar la función de los genes recién descubiertos involucrados en la interferencia del ARN.

Principales métodos:

Cribado para mutaciones de Caenorhabditis elegans con respuestas mejoradas al ARN de doble cadena (dsRNA).
Análisis de complementación genética para identificar mutaciones en eri-6 y eri-7.
Análisis del procesamiento del ARN pre-mensajero (pre-ARNm), incluido el trans-splicing y la edición de adenosina a inosina.
Caracterización de la proteína ERI-6/7 como una helicasa de la superfamilia I.

Principales resultados:

Aislamiento de mutaciones en dos genes adyacentes transcritos de manera divergente, eri-6 y eri-7.
Descubrimiento de que el eri-6 y el eri-7 forman un único ARNm funcional (eri-6/7) a través del trans-splicing.
Evidencia de un intermediario de pre-ARNm de doble cadena formado a través de la edición de adenosina a inosina antes del empalme.
La proteína ERI-6/7, una helicasa, regula negativamente el RNAi exógeno y participa en el RNAi endógeno.

Conclusiones:

El locus del gen eri-6/7 codifica un regulador crucial de las vías de interferencia del ARN.
La edición y el trans-splicing del pre-ARNm nuclear son pasos clave en la maduración del ARNm eri-6/7.
La helicasa ERI-6/7 juega un doble papel en el control tanto del ARN i. extranjero como del auto-derivado.

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