Nonsense suppression by snoRNA-directed RNA pseudouridylation. Depicted is the emerging potential of H/ACA snoRNA-directed RNA pseudouridylation to induce nonsense suppression of an in-frame PTC. (1) A PTC created by a nonsense mutation, which resides upstream of the normal termination codon (NTC), triggers NMD of the PTC-containing transcript. A small fraction of the PTC-containing mRNA may escape NMD and, when translated, may lead to production of a truncated, nonfunctional protein. (2) Delivery of a designer H/ACA snoRNA guides pseudouridine (Ψ) modification of a target uridine within a PTC by the cellular machinery. (3) Pseudouridine within the PTC leads to efficient translational readthrough of the modified PTC, NMD suppression, and increased expression of full-length protein.
