Science

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

M Maximilian Wiesbeck (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) E Emilie L. Alard (Department of Biochemistry, University of Oxford, Oxford, UK.) F Florencia Merino (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) N Niti Chowdhury (Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Neuherberg, Germany.) L Luisa Egert (Institute of Stem Cell Research, Helmholtz Zentrum, German Research Center for Environmental Health, Planegg-Martinsried, Germany.) A Anna Danese (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) S Simon Imhof (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) M Matilde Iraci Borgia (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) A Akshaya Rajan (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) N Nadine Fernandez-Novel Marx (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) E Edina Kepesidis (Institute of Stem Cell Research, Helmholtz Zentrum, German Research Center for Environmental Health, Planegg-Martinsried, Germany.) A Anna Köferle (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) L Luis Miguel Cerron-Alvan (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) F Franziska Vierl (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) T Thi-Tram Truong (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) M Manja Thorwirth (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) L Lorina Bilalli (Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.) J Jovica Ninkovic (Research Unit Central Nervous System Regeneration, Helmholtz Zentrum, Munich, Germany.) R Rico Schieweck (Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.) M Markus Diefenbacher (Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Neuherberg, Germany.) S Stefanie M. Hauck (Metabolomics and Proteomics Core, Helmholtz Centre Munich, German Research Center for Environmental Health, Neuherberg, Germany.) P Paul Trainor (Stowers Institute for Medical Research, Kansas City, MO, USA.) F Faraz K. Mardakheh (Department of Biochemistry, University of Oxford, Oxford, UK.) M Magdalena Götz (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.) S Stefan H. Stricker (Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.)

Abstract

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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Article Details

Journal Science
Volume / Issue Vol. 1, Issue 1
Published July 02, 2026
ISSN 0036-8075
Publisher American Association for the Advancement of Science

Journal Info

Science

American Association for the Advancement of Science
ISSN: 0036-8075 Social Sciences

Authors (25)

M

Maximilian Wiesbeck

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

E

Emilie L. Alard

Department of Biochemistry, University of Oxford, Oxford, UK.

F

Florencia Merino

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

N

Niti Chowdhury

Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Neuherberg, Germany.

L

Luisa Egert

Institute of Stem Cell Research, Helmholtz Zentrum, German Research Center for Environmental Health, Planegg-Martinsried, Germany.

A

Anna Danese

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

S

Simon Imhof

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

M

Matilde Iraci Borgia

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

A

Akshaya Rajan

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

N

Nadine Fernandez-Novel Marx

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

E

Edina Kepesidis

Institute of Stem Cell Research, Helmholtz Zentrum, German Research Center for Environmental Health, Planegg-Martinsried, Germany.

A

Anna Köferle

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

L

Luis Miguel Cerron-Alvan

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

F

Franziska Vierl

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

T

Thi-Tram Truong

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

M

Manja Thorwirth

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

L

Lorina Bilalli

Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.

J

Jovica Ninkovic

Research Unit Central Nervous System Regeneration, Helmholtz Zentrum, Munich, Germany.

R

Rico Schieweck

Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.

M

Markus Diefenbacher

Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Neuherberg, Germany.

S

Stefanie M. Hauck

Metabolomics and Proteomics Core, Helmholtz Centre Munich, German Research Center for Environmental Health, Neuherberg, Germany.

P

Paul Trainor

Stowers Institute for Medical Research, Kansas City, MO, USA.

F

Faraz K. Mardakheh

Department of Biochemistry, University of Oxford, Oxford, UK.

M

Magdalena Götz

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

S

Stefan H. Stricker

Division of Physiological Genomics, Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

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