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Metilación del ARN específico del sitio por una metiltransferasa ribozima
Carolin P M Scheitl1, Mohammad Ghaem Maghami1, Ann-Kathrin Lenz1
1Institut für Organische Chemie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Nature
|October 29, 2020
Resumen
Los investigadores diseñaron una nueva ribozima capaz de metilizar el ARN. Esta ribozima metiltransferasa utiliza un cofactor de molécula pequeña, ofreciendo nuevas ideas sobre el potencial catalítico y las aplicaciones sintéticas del ARN.
Área de la Ciencia:
- Biología molecular
- La bioquímica
- Biología del ARN
Sus antecedentes:
- Las modificaciones post-transcripcionales, incluida la metilación del ARN, son comunes en los ARN codificantes y no codificantes.
- Los nucleótidos metilados en el ARN de transferencia (ARNt) y el ARN ribosomal (ARNr) están altamente conservados.
- Se cree que los cofactores derivados de nucleótidos como la S-adenosilmetionina (SAM) se originan en un mundo de ARN.
Objetivo del estudio:
- Para diseñar una nueva metiltransferasa ribozima.
- Investigar las capacidades catalíticas del ARN en las reacciones de metilación.
- Desarrollar una herramienta sintética para la metilación del ARN específico del sitio.
Principales métodos:
- Se utilizó la selección in vitro para desarrollar una metiltransferasa ribozima.
- Se probó la capacidad de la ribozima para metilizar el ARN utilizando la O6-metilguanina como cofactor.
- Se evaluó el alcance del sustrato de la ribozima modificada.
Principales resultados:
- Se diseñó con éxito una nueva metiltransferasa ribozima.
- La ribozima cataliza la instalación específica del sitio de la 1-metiladenosina en el ARN del sustrato.
- La ribozima demuestra un amplio alcance de secuencia de ARN para la metilación de la adenosina.
Conclusiones:
- El ARN posee un potencial catalítico significativo más allá de la autorreplicación.
- La ribozima diseñada sirve como una herramienta valiosa para la modificación del ARN sintético.
- Este trabajo puede facilitar la evolución in vitro de otras enzimas modificadoras de ARN.
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