Diverse Regulators of Human Ribosome Biogenesis Discovered by Changes in Nucleolar Number

Publication date: 13 February 2018 Source:Cell Reports, Volume 22, Issue 7 Author(s): Katherine I. Farley-Barnes, Kathleen L. McCann, Lisa M. Ogawa, Janie Merkel, Yulia V. Surovtseva, Susan J. Baserga 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. Graphical abstract Teaser Ribosome biogenesis in the nucleolus is essential for cell growth in all eukaryotic cells. Farley-Barnes et al. use an unbiased genome-wide siRNA screen in human cells to discover proteins required to make ribosomes, connecting unexpected pathways to ribosome assem...

Source: Cell Reports - February 24, 2018 Category: Cytology Source Type: research