title: SnoRNA U50 levels are regulated by cell proliferation and rRNA transcription.
abstract: rRNA post transcriptional modifications play a role in cancer development by affecting ribosomal function. In particular, the snoRNA U50, mediating the methylation of C2848 in 28S rRNA, has been suggested as a potential tumor suppressor-like gene playing a role in breast and prostate cancers and B-cell lymphoma. Indeed, we observed the downregulation of U50 in colon cancer cell lines as well as tumors. We then investigated the relationship between U50 and proliferation in lymphocytes stimulated by phytohemagglutinin (PHA) and observed a strong decrease in U50 levels associated with a reduced C2848 methylation. This reduction was due to an alteration of U50 stability and to an increase of its consumption. Indeed, the blockade of ribosome biogenesis induced only an early decrease in U50 followed by a stabilization of U50 levels when ribosome biogenesis was almost completely blocked. Similar results were found with other snoRNAs. Lastly, we observed that U50 modulation affects ribosome efficiency in IRES-mediated translation, demonstrating that changes in the methylation levels of a single specific site on 28S rRNA may alter ribosome function. In conclusion, our results link U50 to the cellular proliferation rate and ribosome biogenesis and these findings may explain why its levels are often greatly reduced in cancers.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant'Orsola-Malpighi University Hospital, Bologna 40138, Italy. annalisa.pacilli@gmail.com
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pacilli
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Davide
authors.initials: D
authors.lastname: Treré
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Montanaro
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D015536:Down-Regulation; D045325:HCT116 Cells; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D016376:Oligonucleotides, Antisense; D010835:Phytohemagglutinins; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar