Abstract

Abstract In the snoRNA host gene SNHG14 , 29 consecutive introns each generate SNORD116, and 48 tandem introns encode SNORD115. Loss of SNORD116 expression, but not of SNORD115, is linked to the neurodevelopmental disease Prader-Willi syndrome. SNORD116 and SNORD115 resemble box C/D small nucleolar RNAs (snoRNAs) but lack known targets. Both were strongly accumulated during neuronal differentiation, but with distinct mechanisms: Increased host-gene expression for SNORD115 and apparent stabilization for SNORD116. For functional characterization we created cell lines specifically lacking the expressed, paternally inherited, SNORD115 or SNORD116 cluster. Analyses during neuronal development indicates changes in RNA stability and protein synthesis. These data suggest that the loss of SNORD116 enhances some aspects of developmental timing of neuronal cells. Altered mRNAs include MAGEL2 , causal in the PWS-like disorder Schaaf-Yang syndrome. Comparison of SNORD115 and SNORD116 mutants identifies small numbers of altered mRNAs and ncRNAs. These are enriched for functions potentially linked to PWS phenotypes and include protocadherins, which are key cell signalling factors during neurodevelopment.