guest ::
| Home > Publications database > Dynamic rRNA Methylation Regulates Translation in the Hematopoietic System and is Essential for Stem Cell Fitness. > print |
| Home > Publications database > Dynamic rRNA Methylation Regulates Translation in the Hematopoietic System and is Essential for Stem Cell Fitness. > print |
| 001 | 305655 | ||
| 005 | 20251106150114.0 | ||
| 024 | 7 | _ | |a 10.1182/blood.2024028300 |2 doi |
| 024 | 7 | _ | |a pmid:41191530 |2 pmid |
| 024 | 7 | _ | |a 0006-4971 |2 ISSN |
| 024 | 7 | _ | |a 1528-0020 |2 ISSN |
| 037 | _ | _ | |a DKFZ-2025-02287 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Rabany, Ofri |b 0 |
| 245 | _ | _ | |a Dynamic rRNA Methylation Regulates Translation in the Hematopoietic System and is Essential for Stem Cell Fitness. |
| 260 | _ | _ | |a Washington, DC |c 2025 |b American Society of Hematology |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1762437660_1579197 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a epub |
| 520 | _ | _ | |a Self-renewal and differentiation are at the basis of hematopoiesis. While it is known that tight regulation of translation is vital for hematopoietic stem cells' (HSCs) biology, the mechanisms underlying translation regulation across the hematopoietic system remain obscure. Here we reveal a novel mechanism of translation regulation in the hematopoietic hierarchy, which is mediated by ribosomal RNA (rRNA) methylation dynamics. Using ultra-low input ribosome-profiling, we characterized cell-type-specific translation capacity during erythroid differentiation. We found that translation efficiency changes progressively with differentiation and can distinguish between discrete cell populations as well as to define differentiation trajectories. To reveal the underlying mechanism, we performed comprehensive mapping of the most abundant rRNA modification - 2'-O-methyl (2'OMe). We found that, like translation efficiency, 2'OMe dynamics followed a distinct trajectory during erythroid differentiation.Genetic perturbation of individual 2'OMe sites demonstrated their distinct roles in modulating proliferation and differentiation. By combining CRISPR screening, molecular and functional analyses, we identified a specific methylation site, 28S-Gm4588, which is progressively lost during differentiation, as a key regulator of HSC self-renewal. We showed that low methylation at this site led to translational skewing, mediated mainly by codon frequency, which promoted differentiation. Functionally, HSCs with diminished 28S-Gm4588 methylation exhibited impaired self-renewal capacity ex-vivo, and loss of fitness in-vivo in bone marrow transplantations.Extending our findings beyond the hematopoietic system, we also found distinct dynamics of 2'OMe profiles during differentiation of non-hematopoietic stem cells. Our findings reveal rRNA methylation dynamics as a general mechanism for cell-type-specific translation, required for cell function and differentiation. |
| 536 | _ | _ | |a 311 - Zellbiologie und Tumorbiologie (POF4-311) |0 G:(DE-HGF)POF4-311 |c POF4-311 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 700 | 1 | _ | |a Ben Dror, Sivan |b 1 |
| 700 | 1 | _ | |a Arafat, Maram |b 2 |
| 700 | 1 | _ | |a Aharoni Levitanus, Hadar |b 3 |
| 700 | 1 | _ | |a Halperin, Yudit |0 0009-0009-7378-4946 |b 4 |
| 700 | 1 | _ | |a Marchand, Virginie |0 0000-0002-8537-1139 |b 5 |
| 700 | 1 | _ | |a Romanovski, Nikolai |b 6 |
| 700 | 1 | _ | |a Ussishkin, Noga |0 0009-0006-6357-7212 |b 7 |
| 700 | 1 | _ | |a Livneh Golany, Maayan |b 8 |
| 700 | 1 | _ | |a Reches, Adi |b 9 |
| 700 | 1 | _ | |a Wexler, Judith |b 10 |
| 700 | 1 | _ | |a Mayorek, Nina |b 11 |
| 700 | 1 | _ | |a Monderer-Rothkoff, Galya |b 12 |
| 700 | 1 | _ | |a Shifman, Sagiv |0 0000-0003-4071-5361 |b 13 |
| 700 | 1 | _ | |a Mâmmer Bouhou, Widad |b 14 |
| 700 | 1 | _ | |a VanInsberghe, Michael |0 0000-0001-8418-4393 |b 15 |
| 700 | 1 | _ | |a Pauli, Cornelius |0 P:(DE-He78)09cd3a09acde3c9d99ac67be925b517c |b 16 |u dkfz |
| 700 | 1 | _ | |a Müller-Tidow, Carsten |b 17 |
| 700 | 1 | _ | |a Karmi, Ola |0 0000-0002-8684-7039 |b 18 |
| 700 | 1 | _ | |a Livneh, Yoav |0 0000-0002-0434-4201 |b 19 |
| 700 | 1 | _ | |a van Oudenaarden, Alexander |b 20 |
| 700 | 1 | _ | |a Motorin, Yuri |0 0000-0002-8018-334X |b 21 |
| 700 | 1 | _ | |a Nachmani, Daphna |b 22 |
| 773 | _ | _ | |a 10.1182/blood.2024028300 |g p. blood.2024028300 |0 PERI:(DE-600)1468538-3 |p nn |t Blood |v nn |y 2025 |x 0006-4971 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 16 |6 P:(DE-He78)09cd3a09acde3c9d99ac67be925b517c |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Krebsforschung |1 G:(DE-HGF)POF4-310 |0 G:(DE-HGF)POF4-311 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Zellbiologie und Tumorbiologie |x 0 |
| 914 | 1 | _ | |y 2025 |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b BLOOD : 2022 |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |d 2024-12-30 |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1190 |2 StatID |b Biological Abstracts |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1110 |2 StatID |b Current Contents - Clinical Medicine |d 2024-12-30 |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2024-12-30 |
| 915 | _ | _ | |a IF >= 20 |0 StatID:(DE-HGF)9920 |2 StatID |b BLOOD : 2022 |d 2024-12-30 |
| 920 | 1 | _ | |0 I:(DE-He78)A350-20160331 |k A350 |l A350 Reguläre Mechanismen der Genexpression |x 0 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-He78)A350-20160331 |
| 980 | _ | _ | |a UNRESTRICTED |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|