Manipulation of protein translation and stem cell self-renewal by CRISPR activation of rRNA transcription
Манипулирование трансляцией белка и самоподдержанием стволовых клеток с помощью активации транскрипции rRNA CRISPR
2026-07-02
SCID: 54.1/srjsgket
Discuss with AI
47S rDNA transcriptionCRISPR activationTAPIRneural stem cell self-renewalrRNA transcription
Figures from the paper
Abstract (AI)
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.
Key Findings
1
Developed TAPIR, a CRISPR-based method to elevate 47S rDNA transcription and thereby increase rRNA levels.
2
Elevated translation via TAPIR promoted neural stem cell self-renewal and proliferation both in vitro and in vivo.
3
TAPIR enabled modeling of disease phenotypes linked to rRNA dysregulation and facilitated partial rescue of those phenotypes.
4
TAPIR-induced rRNA upregulation enlarged nucleolar size and enhanced global protein synthesis, including in rapidly proliferating cells.
5
rRNA levels directly regulate translational output, and protein synthesis capacity can determine mammalian stem cell behavior.
Research Object
Cellular ribosomal RNA (rRNA) levels manipulated via CRISPR-based TAPIR to induce 47S rDNA transcription
Research Subject
Effects of elevated rRNA levels on protein translation capacity, nucleolar size, and stem cell self-renewal and proliferation (including in vitro and in vivo behavior and disease-phenotype modeling/rescue)
Publication Details
Publication Date
2026-07-02
Journal
Publisher
ISSN
Cited by
0
Open access PDF
Access Type
Author Information
Download PDF
Subscribe to digest