Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RPL41 stabilizes ribosome dynamics and supports long-protein homeostasis in mammals

ABSTRACT: Ribosomal protein L41 (RPL41 or eL41) is the smallest ribosomal protein and forms the eukaryote-specific bridge, eB14, near the decoding center; however, its role in mammalian translation remains unclear. In this study, we established RPL41-deficient models of human HEK293T cells and mice to define its function. Cryo-electron microscopy revealed that RPL41 constrains intersubunit conformational dynamics without inducing major local static rearrangements. Loss of RPL41 altered A-site dynamics, slowed elongation, modestly increased amino acid misincorporation, and modestly enhanced readthrough of collision-inducing reporter sequences. Quantitative proteomic analysis suggested that these translational defects compromise long-protein homeostasis, as evidenced by increased insolubility and reduced abundance of long proteins. In vivo, Rpl41−/− mice were viable but exhibited growth retardation and decreased abundance of long proteins in tissues. Our findings reveal a conserved role for RPL41 in maintaining ribosome dynamics and translational fidelity, indicating that RPL41 supports ribosome function and long-protein homeostasis in mammals.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE308359 | GEO | 2026/07/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Znf598-mediated Rps10/eS10 Ubiquitination contributes to the ribosome ubiquitination dynamics during zebrafish development

Project description:The ribosome is a translational apparatus that comprises about 80 ribosomal proteins and four rRNAs. Recent studies reported that ubiquitination of the ribosomal proteins plays a pivotal role in translational control and ribosome-associated quality control (RQC). However, little is known about the dynamics of ribosome ubiquitination under complex biological processes of multicellular organisms. To study ribosome ubiquitination during animal development, we generated a zebrafish strain that expresses a FLAG-tagged ribosomal protein Rpl36/eL36 from its endogenous locus. Combining affinity purification of ribosomes from rpl36-FLAG zebrafish embryos with immunoblotting analysis, we analyzed ribosome ubiquitination during zebrafish development. Our data showed that ubiquitination of ribosomal proteins dynamically changed as development proceeded. We further revealed that Znf598, an E3 ubiquitin ligase that triggers RQC, contributed to the ribosome ubiquitination during zebrafish development. LC-MS/MS analysis and immunoblotting analysis identified lysines 139 of ribosomal protein Rps10/eS10 as pivotal ubiquitination sites on the ribosome during development. Finally, we demonstrated that an Rps10 K139/140R mutation reduced overall ribosome ubiquitination pattern. Collectively, these results reveal dynamics and complexity of ribosome ubiquitination in zebrafish development.

2023-10-11 | PXD039560 | JPOST Repository

Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics

Project description:Ribosome profiling is a widespread tool for studying translational dynamics in human cells. Its central assumption is that ribosome footprint density on a transcript quantitatively reflects protein synthesis. Here, we test this assumption using pulsed-SILAC (pSILAC) high-accuracy targeted proteomics. We focus on multiple myeloma cells exposed to bortezomib, a first-line chemotherapy and proteasome inhibitor. In the absence of drug effects, we found that direct measurement of protein synthesis by pSILAC correlated well with indirect measurement of synthesis from ribosome footprint density. This correlation, however, broke down under bortezomib-induced stress. By developing a statistical model integrating longitudinal proteomic and mRNA-seq measurements, we found that proteomics could directly detect global alterations in translational rate caused by bortezomib; these changes are not detectable by ribosomal profiling alone. Further, by incorporating pSILAC data into a gene expression model, we predict cell-stress specific proteome remodeling events. These results demonstrate that pSILAC provides an important complement to ribosome profiling in measuring proteome dynamics. Timecourse experiment with six points over 48hr after bortezomib exposure in MM.1S myeloma cells. mRNA-seq and ribosome profiling data at each time point.

2017-05-18 | E-GEOD-69047 | biostudies-arrayexpress

Structures of Naked Mole-Rat, Tuco-Tuco, and Guinea Pig Ribosomes: Is rRNA Fragmentation Linked to Translational Fidelity?

Project description:Ribosomes are central to protein synthesis in all organisms. Among mammals, the ribosome functional core is highly conserved. Remarkably, two rodent species, the naked mole-rat (NMR) and tuco-tuco display fragmented 28S rRNA, coupled with high translational fidelity and long lifespan. The unusual ribosomal architecture in the NMR and tuco-tuco has been speculated to be linked to high translational fidelity. Here we show, by single-particle cryo-electron microscopy (cryo-EM), that despite the fragmentation of their rRNA, NMR and tuco-tuco ribosomes retain their core functional architecture. Compared to ribosomes of the guinea pig, a phylogenetically related rodent without 28S rRNA fragmentation, ribosomes of NMR and tuco-tuco exhibit poorly resolved, certain expansion segments. In contrast, the structure of the guinea pig ribosome shows high similarity to human ribosome. Enhanced translational fidelity in the NMR and tuco-tuco may stem from subtle, allosteric effects in dynamics, linked to rRNA fragmentation.

2026-03-12 | GSE306918 | GEO

Genome-wide translational analysis of RAW264 macrophages by ribosome profiling

Project description:Purpose: The aim is to analyze the translational kinetics of the basal and LPS-stimulated conditions of RAW264 macrophages focusing on ribosome density Method: RAW264 macrophages were cultured at 3.0 x 10^5 cells/ml in media (DMEM, 2mM Glutamine, 10% FBS, 100 units penicillin and 100Âµg streptomycin/mL) 24 hours prior to harvest. It was confirmed that the confluency of cells never surpassed 80 ~ 90%. Cell were harvested in their basal state or LPS stimulated condition (100 ng/ml for 30 min) and ribosome profiling (Ribo-Seq) and high-throughput mRNA sequencing (mRNA-Seq) were conducted. Ribosome protected fragments (RPF) were sequenced and the density was normalized by mRNA abundance. Result and conclusion: We discovered where in the ribosome translational arrest ocurs and how this happens. Translational stall was striking at A-site and P-site of ribosomal complex. The other arrest site was observed 3 to 5 residues away from the peptidyl transfer center of the exit tunnel, in which ribosomal density and hydrophobicity showed a significant negative correlation. mRNA and RPF of RAW264 macrophages were deep-sequenced with two independent biological replicates by Ion PGM sequencer

2015-11-01 | E-GEOD-60930 | biostudies-arrayexpress

Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics

2017-05-18 | GSE69047 | GEO

The transcription and translation landscapes during human cytomegalovirus infection reveal novel host-pathogen interactions

Project description:During its long infection cycle, human cytomegalovirus (HCMV) extensively manipulates cellular gene expression to maintain conditions favorable for viral propagation. In order to reveal the signature of cellular genes that are manipulated by HCMV, we measured RNA abundance and rate of protein production through the course of HCMV infection. We characterized changes for most expressed cellular genes and although much of the regulation was transcriptional we uncover diverse and dynamic translational regulation for subsets of host genes, revealing unappreciated coordination in translational control that suggests common regulators Ribosome profiling and mRNA-seq along HCMV infection

2015-11-02 | E-GEOD-69906 | biostudies-arrayexpress

Transcription profiling of S. cerevisiae unfolding response

Project description:The accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR) which is characterised in part by the transcriptional induction of genes involved in assisting protein folding. Translational responses to ER stress have been less well described and here we report on a genome-wide analysis of translational regulation in the response to the ER stress-inducing agent dithiothreitol (DTT) in Saccharomyces cerevisiae. Although the observed polysome profiles were similar under control and ER stress conditions microarray analysis identified transcipt-specific translational regulation. Genes with functions in ribosomal biogenesis and assembly were translationally repressed under ER stress. In contrast mRNAs for known UPR genes, including the UPR transcription factor HAC1, the ER-oxidoreductase ERO1 and the ER-associated protein degradation (ERAD) gene DER1 were enriched in polysomal fractions under ER stress conditions. In addition, we show that splicing of HAC1 mRNA is required for efficient ribosomal loading and that Gcn2p is required for normal HAC1 splicing, so shedding light on the role of this protein kinase in the UPR pathway. Experiment Overall Design: Polyribosomes were extracted from S. cerevisiae cells treated with 2 mM DTT or water (control), and fractionated according to ribosome loading. Following RNA purification from these fractions, for each sub-polysomal and polysomal RNA sample, fractions from three independent extracts per treatment (DTT/control) were pooled.

2008-06-11 | E-GEOD-10091 | biostudies-arrayexpress

Ribosome profiling of early zebrafish embryos -- miRNA-mediated regulation during embryogenesis causes translational repression before mRNA decay

Project description:MicroRNAs regulate gene expression through deadenylation, repression and mRNA decay. However, the contribution of each mechanism in non-steady-state situations remains unclear. We monitored the impact of miR-430 on ribosome occupancy of endogenous mRNAs in wild type and dicer mutants lacking mature miR-430. Our results indicate that miR-430 reduces the number of ribosomes on target mRNAs before causing mRNA decay. Translational repression occurs before complete deadenylation, and disrupting deadenylation using an internal poly(A) tail did not block target repression. Finally, we observe that ribosome density along the length of the target mRNA remains constant, suggesting that translational repression occurs by reducing the initiation rate rather than reducing elongation or causing ribosomal drop-off. In summary, our results show that miR-430 regulates translation initiation before inducing mRNA decay. Time course parallel ribosome profiling and input mRNA quantification in wildtype and MZdicer mutant embryos

2012-03-15 | E-GEOD-34743 | biostudies-arrayexpress

Multifarious translational regulation during replicative aging in yeast

Project description:Protein synthesis is strictly regulated during replicative aging in yeast, but global translational regulation during replicative aging is poorly characterized. To conduct ribosomal profiling during replicative aging, we collected a large number of dividing aged cells using a miniature chemostat aging device. Translational efficiency, defined as the number of ribosome footprints normalized to transcript abundance, was compared between young and aged cells for each gene. We identified more than 700 genes with changes greater than twofold during replicative aging. Increased translational efficiency was observed in genes involved in DNA repair and chromosome organization. Decreased translational efficiency was observed in genes encoding ribosome components, transposon Ty1 and Ty2 genes, transcription factor HAC1 genes associated with the unfolded protein response, genes involved in cell wall synthesis and assembly, and ammonium permease genes. Our results provide a global view of translational regulation during replicative aging, in which the pathways involved in various cell functions are translationally regulated and cause diverse phenotypic changes.

2022-09-25 | GSE203147 | GEO

Double Stranded DNA Breaks and Genome Editing Trigger Ribosome Remodeling and Translational Shutdown

Project description:DNA damage activates a robust transcriptional stress response, but much less is known about how DNA damage impacts translation. The advent of genome editing with Cas9 has intensified interest in understanding cellular responses to DNA damage. Here, we find that DNA double-strand breaks (DSBs), including those induced by Cas9, trigger the loss of ribosomal protein RPS27A from ribosomes via p53-independent proteasomal degradation. Comparisons of Cas9 and dCas9 ribosome profiling and mRNA-seq experiments reveal a global translational response to DSBs that precedes changes in transcript abundance. Our results demonstrate that even a single DSB can lead to altered translational output and ribosome remodeling, suggesting caution in interpreting cellular phenotypes measured immediately after genome editing.

2021-11-15 | GSE122615 | 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