Total RNAseq from patient DM1 cell line
Recently, the repertoire of human small nucleolar ncRNAs (snoRNAs) and their potential functions have been expanded by the discovery of new snoRNAs and mRNA targets, for which snoRNA-guided modifications may influence their stability, translatability, or splicing. We previously identified snoRNAs that are abundant in healthy human muscle progenitors. Here, we showed that SNORA40 and SNORA70 loss-of-function impairs myogenic differentiation. Strikingly, their gain-of-function can rescue the impaired differentiation muscle progenitor cells in Myotonic Dystrophy type 1 (DM1). We identified the CCND3 mRNA, partly located in the nucleolus, as a target of SNORA40 and SNORA70, which are needed for its pseudouridylated status. Expression of the CCND3 protein is required for muscle progenitors to exit the cell cycle when they are induced to differentiation. Here, we revealed that this switch requires SNORA40/70. Finally, we showed that rescuing reduced levels found in DM1 cells restores the expression of CCND3 through pseudouridylation of its mRNA, and ultimately resumes the cell fusion capacity of DM1 muscle progenitors. Overall design: Total RNAseq from patient DM1 cell line