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000182171 1001_ $$aZhou, Fengbiao$$b0
000182171 245__ $$aA dynamic rRNA ribomethylome drives stemness in acute myeloid leukemia.
000182171 260__ $$aPhiladelphia, Pa.$$c2023
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000182171 500__ $$a#EA:A010#LA:A010# / 2023 Feb 6;13(2):332-347
000182171 520__ $$aThe development and regulation of malignant self-renewal remains an unresolved issue. Here, we provide biochemical, genetic, and functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity in vivo. A comprehensive analysis of the rRNA 2'-O-methylation landscape of 94 acute myeloid leukemia (AML) patients revealed dynamic 2'-O-methylation specifically at exterior sites of ribosomes. rRNA 2'-O-methylation pattern is closely associated with AML development stage and LSC gene expression signature. Forced expression of 2'-O-methyltransferase FBL induced an AML stem cell phenotype and enabled engraftment of non-LSC leukemia cells in NSG mice. Enhanced 2'-O-methylation redirected the ribosome translation program towards amino acid transporter mRNAs enriched in optimal codons and subsequently increased intracellular amino acid levels. Methylation at the single site 18S-guanosine 1447 was instrumental for LSC activity. Collectively, our work demonstrates that dynamic 2'-O-Me at specific sites on ribosomal RNAs shifts translational preferences and controls AML-LSC self-renewal.
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000182171 7001_ $$0P:(DE-He78)f086a8a0e493edd2642811ac3248b65b$$aAroua, Nesrine$$b1$$udkfz
000182171 7001_ $$aLiu, Yi$$b2
000182171 7001_ $$00000-0001-6778-5971$$aRohde, Christian$$b3
000182171 7001_ $$00000-0003-4442-377X$$aCheng, Jingdong$$b4
000182171 7001_ $$00000-0002-0138-8583$$aWirth, Anna-Katharina$$b5
000182171 7001_ $$0P:(DE-He78)750580c70861171188621241d0254b3d$$aFijalkowska, Daria$$b6
000182171 7001_ $$00000-0002-2934-1920$$aGöllner, Stefanie$$b7
000182171 7001_ $$aLotze, Michelle$$b8
000182171 7001_ $$00000-0001-8714-205X$$aYun, Haiyang$$b9
000182171 7001_ $$00000-0001-8634-4135$$aYu, Xiaobing$$b10
000182171 7001_ $$aPabst, Caroline$$b11
000182171 7001_ $$aSauer, Tim$$b12
000182171 7001_ $$aOellerich, Thomas$$b13
000182171 7001_ $$00000-0001-8472-5516$$aServe, Hubert$$b14
000182171 7001_ $$00000-0002-3791-0548$$aRollig, Christoph$$b15
000182171 7001_ $$aBornhauser, Martin$$b16
000182171 7001_ $$00000-0003-1241-2048$$aThiede, Christian$$b17
000182171 7001_ $$00000-0002-0748-834X$$aBaldus, Claudia$$b18
000182171 7001_ $$0P:(DE-He78)78bbb829c94caf04ce9b6fb4a5b13edc$$aFrye, Michaela$$b19$$udkfz
000182171 7001_ $$aRaffel, Simon$$b20
000182171 7001_ $$0P:(DE-He78)939d5891259c638c1ab053b1456a578c$$aKrijgsveld, Jeroen$$b21$$udkfz
000182171 7001_ $$0P:(DE-He78)0dc58a3349e4e66a46410a2067e43828$$aJeremias, Irmela$$b22$$udkfz
000182171 7001_ $$00000-0003-4291-3898$$aBeckmann, Roland$$b23
000182171 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b24$$eLast author$$udkfz
000182171 7001_ $$aMuller-Tidow, Carsten$$b25
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