Diverse Regulators of Human Ribosome Biogenesis Discovered by Changes in Nucleolar Number
Katherine I. Farley-Barnes,
Kathleen L. McCann,
Lisa M. Ogawa,
Janie Merkel,
Yulia V. Surovtseva,
Susan J. Baserga
Affiliations
Katherine I. Farley-Barnes
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
Kathleen L. McCann
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, PO Box 12233 MD F3-05, Research Triangle Park, NC 27709, USA
Lisa M. Ogawa
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
Janie Merkel
Yale Center for Molecular Discovery, Yale University, 600 West Campus Drive, West Haven, CT 06516, USA
Yulia V. Surovtseva
Yale Center for Molecular Discovery, Yale University, 600 West Campus Drive, West Haven, CT 06516, USA
Susan J. Baserga
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA; Corresponding author
Summary: Ribosome biogenesis is a highly regulated, essential cellular process. Although studies in yeast have established some of the biological principles of ribosome biogenesis, many of the intricacies of its regulation in higher eukaryotes remain unknown. To understand how ribosome biogenesis is globally integrated in human cells, we conducted a genome-wide siRNA screen for regulators of nucleolar number. We found 139 proteins whose depletion changed the number of nucleoli per nucleus from 2–3 to only 1 in human MCF10A cells. Follow-up analyses on 20 hits found many (90%) to be essential for the nucleolar functions of rDNA transcription (7), pre-ribosomal RNA (pre-rRNA) processing (16), and/or global protein synthesis (14). This genome-wide analysis exploits the relationship between nucleolar number and function to discover diverse cellular pathways that regulate the making of ribosomes and paves the way for further exploration of the links between ribosome biogenesis and human disease.
