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Ribosome biogenesis is dynamically regulated during osteoblast differentiation.
Cynthia L Neben1, Fides D Lay2, Xiaojing Mao1
1Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, United States; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States.
Gene
|November 17, 2016
Summary
Osteoblast differentiation involves dynamic regulation of ribosome biogenesis. Cells transiently silence ribosomal RNA (rRNA) genes by depleting UBF1 and RNA Pol I, coordinating cell fate acquisition.
Area of Science:
- Molecular Biology
- Cell Biology
- Developmental Biology
Background:
- Ribosome biogenesis is crucial for cell growth, proliferation, and differentiation.
- Ribosomal RNA (rRNA) gene transcription by RNA Polymerase I (Pol I) dictates the rate of ribosome biogenesis.
- rRNA gene transcription is a key regulator of cell behavior.
Purpose of the Study:
- To investigate the dynamic regulation of ribosome biogenesis during osteoblast differentiation.
- To elucidate the mechanism by which rRNA gene transcription is controlled in differentiating osteoprogenitor cells.
Main Methods:
- Analysis of nucleolar factor dynamics (UBF1, RNA Pol I) during osteoinduction.
- Assessment of rRNA gene silencing and transcriptional permissibility.
- Quantification of ribosome biogenesis and protein synthesis rates.
Main Results:
- Osteoprogenitor cells transiently silence a subset of rRNA genes during osteoblast differentiation.
- This silencing is mediated by biphasic nucleolar depletion of UBF1 and subsequently RNA Pol I.
- Nucleolar UBF1 depletion correlates with an increase in transcriptionally permissible but silent rRNA genes, reducing ribosome biogenesis and protein synthesis.
Conclusions:
- Ribosome biogenesis is dynamically regulated during osteoblast differentiation through reversible rRNA gene silencing.
- Nucleolar occupancy of UBF1 is a key determinant of rRNA gene transcription levels.
- These regulatory events are coordinated with early osteoblast cell fate acquisition.
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