title: Ribosome biogenesis is dynamically regulated during osteoblast differentiation.
abstract: Changes in ribosome biogenesis are tightly linked to cell growth, proliferation, and differentiation. The rate of ribosome biogenesis is established by RNA Pol I-mediated transcription of ribosomal RNA (rRNA). Thus, rRNA gene transcription is a key determinant of cell behavior. Here, we show that ribosome biogenesis is dynamically regulated during osteoblast differentiation. Upon osteoinduction, osteoprogenitor cells transiently silence a subset of rRNA genes through a reversible mechanism that is initiated through biphasic nucleolar depletion of UBF1 and then RNA Pol I. Nucleolar depletion of UBF1 is coincident with an increase in the number of silent but transcriptionally permissible rRNA genes. This increase in the number of silent rRNA genes reduces levels of ribosome biogenesis and subsequently, protein synthesis. Together these findings demonstrate that fluctuations in rRNA gene transcription are determined by nucleolar occupancy of UBF1 and closely coordinated with the early events necessary for acquisition of the osteoblast cell fate.
authors.affiliation: Center 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.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Neben
authors.affiliation: Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States.
authors.forename: Fides D
authors.initials: FD
authors.lastname: Lay
authors.affiliation: Center 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.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Mao
authors.affiliation: Center 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.
authors.forename: Creighton T
authors.initials: CT
authors.lastname: Tuzon
authors.affiliation: Center 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. Electronic address: amerrill@usc.edu.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Merrill
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D012335:RNA, Ribosomal
keywords: Bone; Osteoblast; Osteoprogenitor; RNA Pol I; Ribosome biogenesis; UBF1; rRNA