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El silenciamiento del ARNm de la lipoxigenasa en la diferenciación eritroide: El complejo regulador 3'UTR controla la
D H Ostareck1, A Ostareck-Lederer, I N Shatsky
1Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117, Heidelberg, Germany.
Cell
|February 24, 2001
Resumen
La traducción de la 15-lipoxigenasa (LOX) está bloqueada en el desarrollo de glóbulos rojos por un complejo específico de ARN. Este complejo impide la unión de las subunidades ribosómicas necesarias para la producción de proteínas.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Reglamento genético Reglamento genético.
- La eritropoiesis es la aparición de la gente.
Sus antecedentes:
- La expresión de la 15-lipoxigenasa (LOX) se silencia traslacionalmente durante el desarrollo temprano de las células precursoras eritroides.
- Este silenciamiento está mediado por un complejo mRNA-proteína que involucra la región 3' no traducida (UTR) y las ribonucleoproteínas nucleares heterogéneas (hnRNP) K y E1.
- Se desconoce el mecanismo preciso por el cual este complejo regulador de 3'UTR inhibe la iniciación de la traducción.
Objetivo del estudio:
- Para dilucidar el mecanismo de silenciamiento traslacional del ARNm LOX en células precursoras de eritroides.
- Para identificar el paso específico en la iniciación de la traducción que es inhibido por el complejo regulador 3'UTR.
- Investigar el potencial de las vías alternativas de iniciación de la traducción.
Principales métodos:
- Análisis del reclutamiento de subunidades ribosomales y exploración en el ARNm LOX in vitro.
- Investigación de la iniciación de la traducción utilizando el IGR-IRES del virus de la parálisis del grillo.
- Pruebas bioquímicas para evaluar la formación del ribosoma 80S.
Principales resultados:
- La subunidad ribosómica 40S puede ser reclutada y escanear el 3'UTR incluso cuando el complejo silenciador está unido.
- La unión de la subunidad ribosómica 60S para formar un ribosoma 80S competente para la traducción es inhibida por el complejo silenciador.
- La iniciación puede ser rescatada por el IGR-IRES del virus de la parálisis del grillo, evitando el complejo inhibidor.
Conclusiones:
- El control traslacional del ARNm LOX se produce en el paso de unión de la subunidad ribosómica 60S.
- El complejo hnRNPs K/E1-3'UTR inhibe específicamente la formación del ribosoma 80S.
- Este hallazgo revela un nuevo mecanismo regulador para la iniciación de la traducción y sugiere posibles objetivos terapéuticos.
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