Fig. 1: Overview of RNU4-2 variants identified in this study.

a, Two-dimensional predicted structure of the interaction between U4 (red) and U6 (orange) snRNAs showing distinct domains. Arrowheads indicate variants identified in this study; P and LP in black, and VUS in gray. The numbers in black within the zoom-in box represent the count of patients with each variant for nucleotide changes that occur more than once. Red and orange numbers refer to the numbering of nucleotides from each snRNA. Red-shaded region, 18-bp critical region; gray-shaded regions, Sm sites. b, Organization of the U4–U6 duplex at the tri-snRNP stage (PDB ID: 6QW6) and close-up views of stem III, RBM42 binding and quasi-pseudoknot regions. Interactions stabilizing these structures, as well as LP/P variants potentially affecting their stability, are represented. Ψ, pseudouridine; m, 2′-O-methyl residues; m6, N6-methyladenosine; ^2,2,7m3Gppp, 2,2,7-trimethylguanosine cap; _mpppG, 5′ guanosine triphosphate cap with γ-monomethyl phosphate.