Faculty, Staff and Student Publications
Language
English
Publication Date
10-14-2022
Journal
Nucleic Acids Research
DOI
10.1093/nar/gkac817
PMID
36161484
PMCID
PMC9561284
PubMedCentral® Posted Date
September 2022
PubMedCentral® Full Text Version
Post-print
Abstract
5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the deposition of m5C at position 4447 on the 28S rRNA. We also find that NOP2/NSUN1 binds to the 5'ETS region of the pre-rRNA transcript and regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs. We provide evidence that NOP2/NSUN1 facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes. Remarkably, expression of both WT and catalytically inactive NOP2/NSUN1 in knockdown background rescues the rRNA processing defects and the stable assembly of box C/D snoRNP complexes, suggesting that NOP2/NSUN1-mediated deposition of m5C on rRNA is not required for ribosome synthesis.
Keywords
5-Methylcytosine, Humans, Nuclear Proteins, RNA Precursors, RNA, Ribosomal, RNA, Ribosomal, 28S, RNA, Small Nucleolar, Ribonucleoproteins, Small Nucleolar, Ribosomes, Saccharomyces cerevisiae Proteins, tRNA Methyltransferases
Published Open-Access
yes
Recommended Citation
Liao, Han; Gaur, Anushri; McConie, Hunter; et al., "Human NOP2/NSUN1 Regulates Ribosome Biogenesis Through Non-Catalytic Complex Formation With Box C/D snoRNPs" (2022). Faculty, Staff and Student Publications. 1255.
https://digitalcommons.library.tmc.edu/uthmed_docs/1255