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La ligasa de ubiquitina ZSWIM8 media la degradación dirigida al objetivo del microARN
Charlie Y Shi1,2,3, Elena R Kingston1,2,3, Benjamin Kleaveland4
1Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|November 13, 2020
Resumen
La degradación dirigida al objetivo del miRNA (TDMD) requiere la ligasa de ubiquitina ZSWIM8 E3, exponiendo los miRNA a la descomposición. Este mecanismo da forma a los niveles de microARN en muchos animales.
Área de la Ciencia:
- Biología molecular
- La genética
- La bioquímica
Sus antecedentes:
- Los microARN (miRNA) regulan la expresión génica al asociarse con las proteínas Argonaute (AGO).
- Mientras que la unión de AGO normalmente protege a los miRNA, ciertas interacciones de ARN objetivo pueden conducir a la degradación del miRNA.
Objetivo del estudio:
- Para aclarar el mecanismo de la degradación del miRNA dirigido al objetivo (TDMD).
- Identificar los actores moleculares involucrados en la TDMD y su papel en la estabilidad del miRNA.
Principales métodos:
- Se investigó el papel de la ZSWIM8 Cullin-RING E3 ubiquitina ligasa en la DMT.
- Se han realizado estudios de pérdida de función en células de mamíferos, moscas y nematodos.
Principales resultados:
- La TDMD requiere la ligasa ubiquitina ZSWIM8 Cullin-RING E3.
- Se propuso un modelo en el que la proteólisis AGO dirigida al objetivo expone los miARN a la degradación.
- ZSWIM8 acelera la degradación de muchos miRNA de corta duración en animales bilaterales.
Conclusiones:
- La ubiquitina ligasa ZSWIM8 E3 es un regulador clave de la TDMD.
- Esta vía influye significativamente en las vidas medias del miRNA y en la regulación de los genes en los animales.
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