학술논문

Diverse Regulators of Human Ribosome Biogenesis Discovered by Changes in Nucleolar Number
Document Type
article
Source
Cell Reports, Vol 22, Iss 7, Pp 1923-1934 (2018)
Subject
ribosome biogenesis
nucleolus
RNAi screen
genome-wide
Biology (General)
QH301-705.5
Language
English
ISSN
2211-1247
Abstract
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.