FUS modulates the level of ribosomal RNA modifications by regulating a subset of snoRNA expression [Small RNA seq]

FUS is a nucleocytoplasmic protein involved in many processes such as RNA transport, translation, and metabolism as well as genomic maintenance. FUS mutations are found in several neurodegenerative diseases. We find that FUS knockout (KO) and FUS mutation affects the expression of many C/D box snoRNAs, H/ACA box snoRNAs and scaRNAs. snoRNAs notably serve as adaptors for the 2'-O-methylation (2'-O-me) and pseudouridylation of ribosomal RNA (rRNA). We carried out small RNA sequencing and analyzed the impact on ribosomal RNA 2'-O-methylation and pseudouridylation using RiboMeth-Seq and HydraPsiSeq in FUS knock-out model cell lines (HEK293T FUS KO cells and SH-SY5Y (neuroblastoma) FUS KO cells as well as SH-SY5Y cells with FUS R495X mutation).