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A non-translational role of threonyl-tRNA synthetase in regulating JNK signaling during myogenic differentiation.
Dai, Chong; Reyes-Ordoñez, Adriana; You, Jae-Sung; Chen, Jie.
Afiliación
  • Dai C; Department of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Reyes-Ordoñez A; Department of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • You JS; Department of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Chen J; Department of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
FASEB J ; 35(10): e21948, 2021 10.
Article en En | MEDLINE | ID: mdl-34569098
Aminoacyl-tRNA synthetases (aaRSs) are house-keeping enzymes that are essential for protein synthesis. However, it has become increasingly evident that some aaRSs also have non-translational functions. Here we report the identification of a non-translational function of threonyl-tRNA synthetase (ThrRS) in myogenic differentiation. We find that ThrRS negatively regulates myoblast differentiation in vitro and injury-induced skeletal muscle regeneration in vivo. This function is independent of amino acid binding or aminoacylation activity of ThrRS, and knockdown of ThrRS leads to enhanced differentiation without affecting the global protein synthesis rate. Furthermore, we show that the non-catalytic new domains (UNE-T and TGS) of ThrRS are both necessary and sufficient for the myogenic function. In searching for a molecular mechanism of this new function, we find the kinase JNK to be a downstream target of ThrRS. Our data further reveal MEKK4 and MKK4 as upstream regulators of JNK in myogenesis and the MEKK4-MKK4-JNK pathway to be a mediator of the myogenic function of ThrRS. Finally, we show that ThrRS physically interacts with Axin1, disrupts Axin1-MEKK4 interaction and consequently inhibits JNK signaling. In conclusion, we uncover a non-translational function for ThrRS in the maintenance of homeostasis of skeletal myogenesis and identify the Axin1-MEKK4-MKK4-JNK signaling axis to be an immediate target of ThrRS action.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Treonina-ARNt Ligasa / Sistema de Señalización de MAP Quinasas / Desarrollo de Músculos / Proteínas Quinasas JNK Activadas por Mitógenos Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Treonina-ARNt Ligasa / Sistema de Señalización de MAP Quinasas / Desarrollo de Músculos / Proteínas Quinasas JNK Activadas por Mitógenos Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos