| http://purl.uniprot.org/citations/36259929 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36259929 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36259929 | http://www.w3.org/2000/01/rdf-schema#comment | "The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, and functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity in vivo. A comprehensive analysis of the rRNA 2'-O-methylation landscape of 94 patients with acute myeloid leukemia (AML) revealed dynamic 2'-O-methylation specifically at exterior sites of ribosomes. The rRNA 2'-O-methylation pattern is closely associated with AML development stage and LSC gene expression signature. Forced expression of the 2'-O-methyltransferase fibrillarin (FBL) induced an AML stem cell phenotype and enabled engraftment of non-LSC leukemia cells in NSG mice. Enhanced 2'-O-methylation redirected the ribosome translation program toward amino acid transporter mRNAs enriched in optimal codons and subsequently increased intracellular amino acid levels. Methylation at the single site 18S-guanosine 1447 was instrumental for LSC activity. Collectively, our work demonstrates that dynamic 2'-O-methylation at specific sites on rRNAs shifts translational preferences and controls AML LSC self-renewal.SignificanceWe establish the complete rRNA 2'-O-methylation landscape in human AML. Plasticity of rRNA 2'-O-methylation shifts protein translation toward an LSC phenotype. This dynamic process constitutes a novel concept of how cancers reprogram cell fate and function. This article is highlighted in the In This Issue feature, p. 247."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.org/dc/terms/identifier | "doi:10.1158/2159-8290.cd-22-0210"xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.org/dc/terms/identifier | "doi:10.1158/2159-8290.cd-22-0210"xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Cheng J."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Cheng J."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Krijgsveld J."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Krijgsveld J."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Rohde C."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Rohde C."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Yu X."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Yu X."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Zhou F."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Zhou F."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Beckmann R."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Beckmann R."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Muller-Tidow C."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Muller-Tidow C."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Serve H."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Serve H."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Pabst C."xsd:string |
| http://purl.uniprot.org/citations/36259929 | http://purl.uniprot.org/core/author | "Pabst C."xsd:string |