Role of neddylation in translational control of Schwann cell myelination

• Autores: Cecilia Huarte Sebastián
• Directores de la Tesis: Ashwin Woodhoo (dir. tes.)
• Lectura: En la Universidade de Santiago de Compostela ( España ) en 2025
• Idioma: inglés
• Tribunal Calificador de la Tesis: Carmen Rivas Vázquez (presid.), Miguel Angel Fidalgo Pérez (secret.), Sergio Velasco Aviles (voc.)
• Programa de doctorado: Programa de Doctorado en Neurociencia y Psicología Clínica por la Universidad de A Coruña; la Universidad de Santiago de Compostela y la Universidad de Vigo
• Enlaces
  • Tesis en acceso abierto en: MINERVA
• Resumen

  • Schwann cells are responsible for the formation of myelin sheaths around axons in the peripheral nervous system, enabling efficient nerve impulse transmission while also providing structural and metabolic support to axons. Although the transcriptional and epigenetic control of myelination have been extensively studied, changes at the mRNA level alone do not fully account for the Schwann cell differentiation and myelination, highlighting the importance of post-transcriptional regulation in this process. Through combined transcriptome and translatome analyses, we show that genes involved in translation, including ribosomal proteins and translation factors, are coordinately regulated at both the transcriptional and translational levels during Schwann cell differentiation. Furthermore, our study demonstrates the role of neddylation, a post-translational modification, in regulation of protein synthesis during myelination. Here, we demonstrate that neddylation contributes to the formation of a specialized ribosome necessary for the synthesis of proteins involved in Schwann cell differentiation. This occurs through the modification of the translation machinery by NEDD8, the regulation of the ribosomal protein composition, and the modulation of levels and activity of initiation and elongation factors. Thus, neddylation confers specificity to the ribosome, enabling selective translation of particular mRNAs in Schwann cells, while also modulating translational parameters such as the translational rate. Based on these findings, we propose that Schwann cells employ a specific translational program characterized by a low translational rate and the selective inhibition of a subset of mRNAs, which facilitates their exit from the proliferative state and differentiation into myelinating Schwann cells.