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Wiesbeck, M. ; Alard, E.* ; Merino, F.L. ; Chowdhury, N. ; Egert, L. ; Danese, A. ; Imhof, S.* ; Borgia, M.I.* ; Rajan, A.* ; Marx, N.F.* ; Kepesidis, E. ; Köferle, A.* ; Cerron-Alvan, L.M.* ; Vierl, F. ; Truong, T.-T. ; Thorwirth, M. ; Bilalli, L.* ; Ninkovic, J. ; Schieweck, R.* ; Diefenbacher, M. ; Hauck, S.M. ; Trainor, P.A.* ; Mardakheh, F.K.* ; Götz, M. ; Stricker, S.H.

Manipulation of protein translation and stem cell self-renewal by CRISPR activation of rRNA transcription.

Science 393:eaeh1348 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Ribosomal RNA (rRNA) transcription rates vary during development, and their dysregulation is linked to diseases such as cancer and ribosomopathies. Owing to their high abundance and genomic redundancy, the functional significance of rRNA-levels remains unclear. Here, we developed TAPIR (Targeted Activation of Protein Translation), a CRISPR-based approach to elevate rRNA-levels by inducing 47S rDNA transcription. TAPIR increased nucleolar size and enhanced protein synthesis, even in rapidly proliferating cells. In neural stem cells, elevated translation promoted self-renewal and proliferation in vitro and in vivo. Furthermore, TAPIR enabled the modeling and partial rescue of associated disease phenotypes. Our findings revealed that rRNA-levels directly regulate translational output and that protein synthesis capacity can act as a key determinant of mammalian stem cell behavior.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Transcription (linguistics) ; Crispr ; Stem Cell ; Ribosomal Rna ; Protein Biosynthesis ; Messenger Rna ; Translation (biology) ; Ribosomal Protein ; Rna; Spacer Promoters; I Transcription; Polymerase I; Dna; Nucleolus; Pluripotency; Enhancement; Biogenesis; Elongation; Inhibition
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 393, Issue: 6816, Pages: , Article Number: eaeh1348 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
Institute of Lung Health and Immunity (LHI)
Research Unit Central Nervous System Regeneration (CNSR)
Core Facility Metabolomics and Proteomics (CF-MPC)
Grants Fritz Thyssen Foundation
Stowers Institute for Medical Research
The iNeuron
Frontiers in Research Fund (NFRF) Transformation grant through Social Sciences and Humanities Research Council of Canada (SSHRC)
Frontiers in Research Fund (NFRF) Transformation grant through Natural Sciences and Engineering Research Council of Canada and Social Sciences (NSERC)
Frontiers in Research Fund (NFRF) Transformation grant through Canadian Institutes of Health Research (CIHR)
EU/EIC (European Innovation Council) project REGENERAR
Epiadapt
DFG networks SFB 1064
Munich Cluster for Systems Neurology (SyNergy)
Cancer Research UK Programme Foundation Award

Impulse and Networking Fund of the Helmholtz Association (Helmholtz Excellence Network BioEM)
Cluster for Systems Neurology
German Research Foundation TRR274
Canadian federal funding agency (SSHRC)
Canadian federal funding agency (NSERC)
Canadian federal funding agency (CIHR)
New Frontiers in Research Fund Transformation grant
European Research Council (advanced grant NeuroCentro)
DKH
DFG funding (German Research Foundation)
German Research Foundation