Fig. 6.

Schematic illustration of the proposed TyrRS mode of action. TyrRS enters the nucleus and engages with different interaction partners, including transcription factors. CMT-causing mutations do not affect the nuclear translocation of TyrRS. However, when the mutant protein enters the nucleus, these interactions are enhanced or perturbed and new interactions may be formed, leading to dysregulation of the transcriptional machinery. As demonstrated in a Drosophila model, the dysregulation can be alleviated by inhibiting the nuclear entry of TyrRS pharmacologically or genetically