Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Binding to the Ribosome by Eukaryotic Initiation Factor 4B Drives Yeast Translational Control in Response to Urea

ABSTRACT: The yeast eukaryotic initiation factor 4B binds the 40S subunit in translation preinitiation complexes (PICs) and promotes mRNA binding. Here we have compared the effects of disrupting eIF4B RNA- and ribosome-binding domains under ~1400 growth conditions. The RNA-binding RRM was dispensable for stress responses, but ribosome binding stimulated by the NTD promoted growth in response to a number of stressors through changes in translation. In particular, the NTD confers a strong growth advantage in the presence of the denaturing reagent, urea, and a number of osmolytes that require robust cellular integrity for survival. Ribosome profiling of cells with and without the NTD of eIF4B reveals changes in translation of mRNAs containing longer than average and highly structured 5-prime untranslated regions both normally, and in response to urea exposure. Because these changes require 40S binding, our results suggest eIF4B regulates mRNA recruitment as a part of the scanning PIC, rather than by activating isolated mRNPs prior to ribosome binding. This analysis indicates the cellular response to urea in yeast includes a translational component, driven by increased translation of mRNAs encoding proteins associated with the cellular periphery, and highlights the importance of the general translation factor eIF4B in adapting to external conditions.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE139097 | GEO | 2020/04/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Stress-induced translation inhibition through release of 40S scanning initiation factors

Project description:Cellular responses to environmental stress are frequently mediated by RNA-binding proteins (RBPs). Here, we examined global RBP dynamics in Saccharomyces cerevisiae in response to glucose starvation and heat shock. Each stress induced rapid remodeling of the RNA-protein interactome, without corresponding changes in RBP abundance. Consistent with general translation shutdown, ribosomal proteins contacting the mRNA showed decreased RNA-association. Among translation components, RNA-association was most reduced for initiation factors involved in 40S scanning (eIF4A, eIF4B, and Ded1), indicating a common mechanism of translational repression. In unstressed cells, eIF4A, eIF4B, and Ded1 primarily targeted the 5′-ends of mRNAs. Following glucose withdrawal, 5’-binding was abolished within 30sec, explaining the rapid translation shutdown, but mRNAs remained stable. Heat shock induced progressive loss of 5’ RNA-binding by initiation factors over ~16min. Translation shutoff provoked selective 5′-degradation of mRNAs encoding translation-related factors, mediated by Xrn1. These results reveal mechanisms underlying translational control of gene expression during stress.

2020-06-08 | GSE148166 | GEO

40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling

Project description:The recycling of ribosomes at stop codons for use in further rounds of translation is critical for efficient protein synthesis. Removal of the 60S subunit is catalyzed by the ATPase Rli1 (ABCE1) while removal of the 40S is thought to require Tma64 (eIF2D), Tma20 (MCT-1), and Tma22 (DENR). However, it remains unclear how these Tma proteins cause 40S removal and control reinitiation of downstream translation. Here we developed an enhanced 40S ribosome footprinting strategy to directly observe intermediate steps of ribosome recycling in cells. Deletion of the genes encoding these Tma proteins resulted in broad accumulation of unrecycled 40S subunits at stop codons, directly establishing their role in 40S recycling. Furthermore, the Tma20/Tma22 heterodimer was responsible for a majority of 40S recycling events while Tma64 played a minor role. Introduction of an autism-associated mutation into TMA22 resulted in a loss of 40S recycling activity, linking ribosome recycling and neurological disease.

2021-03-01 | GSE145904 | GEO

Small and large ribosomal subunit deficiencies lead to distinct gene expression signatures that reflect cellular growth rate

Project description:Levels of the ribosome, the conserved molecular machine that mediates translation, are tightly linked to cellular growth rate. In humans, ribosomopathies are diseases associated with cell-type-specific pathologies and reduced ribosomal protein (RP) levels. Because gene expression defects resulting from ribosome deficiency have not yet been experimentally defined, we systematically probed mRNA, translation, and protein signatures that were either unlinked or linked to cellular growth rate in RP-deficient yeast cells. Ribosome concentration was seen to be associated with translation of gene sub-classes, and profound general secondary effects of RP loss on the spectrum of cellular mRNAs were seen. Among these effects, growth-defective 60S mutants increased synthesis of proteins involved in proteasome-mediated degradation, whereas 40S mutants accumulated mature 60S subunits and increased translation of ribosome biogenesis genes. These distinct signatures of protein synthesis suggest intriguing and currently mysterious differences in the cellular consequences of deficiency for small and large ribosomal subunits.

2018-11-29 | GSE121189 | GEO

Stress-induced translation inhibition through displacement of scanning initiation factors

Project description:Cellular responses to environmental stress are frequently mediated by RNA-binding proteins (RBPs). Here, we examined global RBP dynamics in Saccharomyces cerevisiae in response to glucose starvation and heat shock. Each stress induced rapid remodeling of the protein:RNA interactome, without corresponding changes in RBP abundance. Consistent with general translation shutdown, ribosomal proteins contacting the mRNA showed decreased RNA-association. Among translation components, RNA-association was most reduced for initiation factors involved in 40S scanning (eIF4A, eIF4B, and Ded1), indicating a common mechanism of translational repression. In unstressed cells, eIF4A, eIF4B, and Ded1 primarily targeted the 5′-ends of mRNAs. Following glucose withdrawal, mRNAs remained stable, but 5’-binding was abolished within 30sec, explaining the rapid translation shutdown. Heat shock induced progressive loss of 5’ RNA-binding by initiation factors over ~16min, and translation shutoff provoked 5′-degradation by Xrn1, selectively for mRNAs encoding translation-related factors. These results reveal mechanisms underlying translational control of gene expression during stress.

2020-10-13 | PXD019141 | Pride

Small and large ribosomal subunit deficiencies lead to distinct gene expression signatures that reflect cellular growth rate

2018-10-12 | MSV000083033 | MassIVE

Hcr1/eIF3j is a 60S ribosomal subunit recycling accessory factor in vivo

Project description:Hcr1/eIF3j is a sub-stoichiometric subunit of eukaryotic initiation factor 3 (eIF3) that can dissociate the post-termination 40S ribosomal subunit from mRNA in vitro. We examined this ribosome recycling role in vivo by ribosome profiling and reporter assays and found that loss of Hcr1 led to reinitiation of translation in 3’UTRs, consistent with a defect in recycling. However, the defect appeared to be in recycling of the 60S subunit, rather than the 40S subunit, because reinitiation did not require an AUG codon and was suppressed by overexpression of the 60S dissociation factor Rli1/ABCE1. Consistent with a 60S recycling role, overexpression of Hcr1 could not compensate for loss of 40S recycling factors Tma64/eIF2D and Tma20/MCT-1. Intriguingly, loss of Hcr1 triggered higher expression of RLI1 via an apparent feedback loop. These findings suggest Hcr1/eIF3j is recruited to ribosomes at stop codons and may coordinate the transition to a new round of translation.

2019-05-23 | GSE124204 | GEO

The 40S-LARP1 complex reprograms the cellular translatome upon mTOR inhibition to preserve the protein synthetic capacity

Project description:Ribosomes execute the transcriptional program in every cell. Critical to sustain nearly all cellular activities, ribosome biogenesis requires the translation of ~200 factors of which 80 are ribosomal proteins (RPs). As ribosome synthesis depends on RP mRNAs translation, a priority within the translatome architecture should exist to ensure the preservation of ribosome biogenesis capacity, particularly under adverse growth conditions. Here we show that under critical metabolic constraints characterized by mTOR inhibition, LARP1 complexed with the 40S subunit protects from ribophagy the mRNAs regulon for ribosome biogenesis and protein synthesis, acutely preparing the translatome to promptly resume ribosomes production after growth conditions return permissive. Characterizing the LARP1-protected translatome revealed a set of 5’TOP transcript isoforms other than RPs involved in energy production and in mitochondrial function, among other processes, indicating that the mTOR-LARP1-5’TOP axis acts at the translational level as a primary guardian of the cellular anabolic capacity

2021-10-30 | GSE186779 | GEO

The E3 SUMO ligase Mms21 controls ribosome biogenesis

Project description:The budding yeast E3 SUMO ligase Mms21, a component of the Smc5-6 complex, regulates sister chromatid cohesion, DNA replication, and DNA repair. We identify a role for Mms21 in ribosome biogenesis. The mms21RINGD mutant exhibits reduced rRNA production, nuclear accumulation of 60S and 40S ribosomal proteins, and elevated Gcn4 translation. Genes involved in ribosome biogenesis and translation are down-regulated in the mms21RINGD mutant. Examining gene expression profile of mms21RINGD mutant compared to wild-type by RNA Seq using Ilumina sequencing

2015-06-13 | E-GEOD-69826 | biostudies-arrayexpress

eIF4B preferentially stimulates translation of long mRNAs with structured 5’UTRs and low closed-loop potential but weak dependence on eIF4G

Project description:DEAD-box RNA helicases eIF4A and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. eIF4B is a cofactor for eIF4A but might also function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. However, either eliminating eIF4B or inactivating eIF4A preferentially impacts mRNAs with longer, more structured 5’UTRs. These findings reveal an eIF4A-independent role for eIF4B in addition to its function as eIF4A cofactor in promoting PIC attachment or scanning on structured mRNAs. eIF4B, eIF4A, and Ded1 mutations also preferentially impair translation of longer mRNAs in a fashion mitigated by the ability to form closed-loop mRNPs via eIF4F-Pab1 association, suggesting cooperation between closed-loop assembly and eIF4B/helicase functions. Remarkably, depleting eIF4G, the scaffold subunit of eIF4F, preferentially impacts short mRNAs with strong closed-loop potential and unstructured 5’UTRs, exactly the opposite features associated with hyperdependence on the eIF4B/helicases. We propose that short, highly efficient mRNAs preferentially depend on the stimulatory effects of eIF4G-dependent closed-loop assembly.

2016-05-27 | GSE81966 | GEO

Analysis of Ribosome Protected Fragments of mRNAs from yeast strains either expressing Rio1p or depleted of Rio1p

Project description:mRNAs bound by ribosomes from yeast cells were analysed in order to determine the exact position of ribosomes in the presence or absence of Rio1p. Beside total Ribosome Protected Fragments (RPFs), RPFs from mRNAs protected by immature pre-40S pre-ribosomes was also analysed. The analysis showed that immature 40S ribosomes can carry out translation and their premature entry into translation is hindered by Rio1p.

2017-08-16 | GSE98333 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data