Research progress of RNA pseudouridine modification in nervous system.

ABSTRACT

Recent advances of pseudouridine (Ψ, 5-ribosyluracil) modification highlight its crucial role as a post-transcriptional regulator in gene expression and its impact on various RNA processes. Ψ synthase (PUS), a category of RNA-modifying enzymes, orchestrates the pseudouridylation reaction. It can specifically recognize conserved sequences or structural motifs within substrates, thereby regulating the biological function of various RNA molecules accurately. Our comprehensive review underscored the close association of PUS1, PUS3, PUS7, PUS10, and dyskerin PUS1 with various nervous system disorders, including neurodevelopmental disorders, nervous system tumors, mitochondrial myopathy, lactic acidosis and sideroblastic anaemia (MLASA) syndrome, peripheral nervous system disorders, and type II myotonic dystrophy. In light of these findings, this study elucidated how Ψ strengthened RNA structures and contributed to RNA function, thereby providing valuable insights into the intricate molecular mechanisms underlying nervous system diseases. However, the detailed effects and mechanisms of PUS on neuron remain elusive. This lack of mechanistic understanding poses a substantial obstacle to the development of therapeutic approaches for various neurological disorders based on Ψ modification.