Imprinted small nucleolar RNAs: Missing link in development and disease?

The 14q32.2 (DLK1-DIO3) and 15q11-q13 (SNURF-SNRPN) imprinted gene loci harbor the largest known small nucleolar RNA clusters expressed from the respective maternal and paternal alleles. Recent studies have demonstrated significant roles for the 15q11-q13 located SNORD115-SNORD116 C/D box snoRNAs in Prader-Willi syndrome (PWS), a neurodevelopmental disorder.

FUS regulates a subset of snoRNA expression and modulates the level of rRNA modifications.

FUS is a multifunctional protein involved in many aspects of RNA metabolism, including transcription, splicing, translation, miRNA processing, and replication-dependent histone gene expression. In this work, we show that FUS depletion results in the differential expression of numerous small nucleolar RNAs (snoRNAs) that guide 2'-O methylation (2'-O-Me) and pseudouridylation of specific positions in ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). Using RiboMeth-seq and HydraPsiSeq for the profiling of 2'-O-Me and pseudouridylation status of rRNA species, we demonstrated considerable hypermodification at several sites in HEK293T and SH-SY5Y cells with FUS knockout (FUS KO) compared to wild-type cells.

The Novel Role of hnRNP UL1 in Human Cell Nucleoli.

hnRNP UL1 plays an important role in cell nuclei, where it is recruited to DNA damage sites and is involved in the repair of DNA double-strand breaks. Furthermore, this protein is known as a transcriptional repressor of RNA polymerase II genes. In the present study, we have shown that hnRNP UL1 is also localized in the nucleoli of human cells.