Genome-wide RNAi screen identifies novel players in human 60S subunit biogenesis including key enzymes of polyamine metabolism
OPEN ACCESS
Author / Producer
Date
2022-03-21
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Abstract
Ribosome assembly is an essential process that is linked to human congenital diseases and tumorigenesis. While great progress has been made in deciphering mechanisms governing ribosome biogenesis in eukaryotes, an inventory of factors that support ribosome synthesis in human cells is still missing, in particular regarding the maturation of the large 60S subunit. Here, we performed a genome-wide RNAi screen using an imaging-based, single cell assay to unravel the cellular machinery promoting 60S subunit assembly in human cells. Our screen identified a group of 310 high confidence factors. These highlight the conservation of the process across eukaryotes and reveal the intricate connectivity of 60S subunit maturation with other key cellular processes, including splicing, translation, protein degradation, chromatin organization and transcription. Intriguingly, we also identified a cluster of hits comprising metabolic enzymes of the polyamine synthesis pathway. We demonstrate that polyamines, which have long been used as buffer additives to support ribosome assembly in vitro, are required for 60S maturation in living cells. Perturbation of polyamine metabolism results in early defects in 60S but not 40S subunit maturation. Collectively, our data reveal a novel function for polyamines in living cells and provide a rich source for future studies on ribosome synthesis.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
50 (5)
Pages / Article No.
2872 - 2888
Publisher
Oxford University Press
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Organisational unit
03543 - Kutay, Ulrike / Kutay, Ulrike
08839 - Zamboni, Nicola (Tit.-Prof.)
02891 - ScopeM / ScopeM
Notes
Funding
166565 - Ribosome synthesis in mammalian cells (SNF)