Molecular functions and therapeutic applications of Ψ modification in mRNAs. (A) mRNA Ψ modifications are catalyzed by various PUSs, including PUS1, PUS1L, PUS3, PUS7, PUS7L, TRUB1, TRUB2, RPUSD4, and DKC1. (B) Ψ impacts multiple facets of mRNA processing and metabolism, such as the local mRNA secondary structure, translation, pre-mRNA splicing, and mRNA stability. Ψ modifications in UAG, UGA, and UAA stop codons lead to stop codon readthrough. Ψ in pre-mRNA can affect the splicing machinery, thereby regulating alternative splicing. Ψs in human mRNAs have been shown to stabilize mRNAs. (C) snoRNA-guided pseudouridylation is emerging as a promising RNA-editing technique for mediating premature termination codon (PTC) readthrough in contexts relevant to diseases. The incorporation of m1Ψ into mRNA vaccines is utilized to enhance their effectiveness as a therapeutic tool.
