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mTORC1 y la regeneración muscular están reguladas por el polipéptido SPAR codificado por LINC00961

Akinobu Matsumoto¹, Alessandra Pasut¹, Masaki Matsumoto²

¹Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

|December 27, 2016

Resumen

Los investigadores descubrieron un polipéptido oculto, SPAR, codificado por el ARN largo no codificante LINC00961. SPAR regula la activación de mTORC1 por los aminoácidos, crucial para la regeneración muscular después de una lesión.

Área de la Ciencia:

Biología molecular
La genética
Biología celular

Sus antecedentes:

Los ARN largos no codificantes (ARNlnc) son cada vez más reconocidos para funciones más allá de las funciones no codificantes.
Algunos lncRNA contienen pequeños marcos de lectura abiertos (ORF) que se pueden traducir en polipéptidos funcionales.
La importancia biológica de estos polipéptidos codificados por lncRNA sigue siendo en gran medida inexplorada.

Objetivo del estudio:

Identificar y caracterizar funcionalmente un nuevo polipéptido codificado por el lncRNA LINC00961.
Para aclarar el papel de este polipéptido en las vías de señalización celular y la regeneración de tejidos.

Principales métodos:

Identificación y caracterización de un nuevo polipéptido (SPAR) de LINC00961.
Ensayos bioquímicos para determinar la localización y las interacciones de SPAR (por ejemplo, con v-ATPasa).
Edición del gen CRISPR/Cas9 para crear modelos de ratones knockout específicos de SPAR.
Estudios in vivo para evaluar la regeneración muscular después de una lesión aguda.

Principales resultados:

Se identificó un polipéptido conservado, SPAR, de LINC00961, localizado en los endosomas / lisosomas tardíos.
SPAR interactúa con la v-ATPasa y regula negativamente la activación de mTORC1 estimulada por los aminoácidos.
Los ratones con SPAR knockout presentan una mayor activación de mTORC1 y una mejor regeneración muscular tras una lesión.
La expresión del LncRNA LINC00961 está regulada a la baja en el músculo esquelético después de la lesión.

Conclusiones:

SPAR, un nuevo polipéptido codificado por lncRNA, proporciona un mecanismo para ajustar la activación de mTORC1 en respuesta a la disponibilidad de aminoácidos.
Esta vía es crítica para la regeneración muscular eficiente después de una lesión.
Los lncRNA pueden codificar pequeños polipéptidos que modulan los procesos biológicos fundamentales para las necesidades específicas del tejido.

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