Zhou et al. 2022 (PRJNA769267)
General Details
Title | The dynamic rRNA ribomethylome drives stemness in acute myeloid leukemia [ribosome profiling] |
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Organism | Homo sapiens |
Number of Samples | 4 |
Release Date | 2021/10/07 00:00 |
Sequencing Types | |
Protocol Details |
Study Links
GWIPS-viz | Trips-Viz | RiboCrypt |
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Repository Details
SRA | SRP340351 |
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ENA | SRP340351 |
GEO | |
BioProject | PRJNA769267 |
Publication
Title | |
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Authors | Zhou F,Aroua N,Liu Y,Rohde C,Cheng J,Wirth AK,Fijalkowska D,Göllner S,Lotze M,Yun H,Yu X,Pabst C,Sauer T,Oellerich T,Serve H,Röllig C,Bornhäuser M,Thiede C,Baldus C,Frye M,Raffel S,Krijgsveld J,Jeremias I,Beckmann R,Trumpp A,Müller-Tidow C |
Journal | Cancer discovery |
Publication Date | 2023 Feb 6 |
Abstract | 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. We 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. ©2022 The Authors; Published by the American Association for Cancer Research. |
PMC | PMC9900322 |
PMID | 36259929 |
DOI |
Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | RiboCrypt | Reads | BAM | BigWig (F) | BigWig (R) | ||
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SRR16230267 | PRJNA769267 | Homo sapiens | ![]() |
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SRR16230268 | PRJNA769267 | Homo sapiens | ![]() |
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SRR16230269 | PRJNA769267 | Homo sapiens | ![]() |
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SRR16230270 | PRJNA769267 | Homo sapiens | ![]() |
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Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | RiboCrypt | Reads | BAM | BigWig (F) | BigWig (R) |
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