Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

THP-1 data for:Ribosome dynamics orchestrate mRNA stability and translation across natural and synthetic systems

ABSTRACT: The dynamic interplay between ribosomes and mRNAs plays a central role in gene expression regulation, balancing protein synthesis and mRNA stability. However, traditional methods capturing static ribosome occupancy fail to resolve the temporal dynamics governing these processes. Here, we introduce Temporal Ribosome Density Profiling (TRiP), which combines metabolic RNA labeling and polysome sequencing to map ribosome density dynamics across the mRNA lifespan. TRiP reveals a striking temporal symmetry conserved across cell types: gene-specific ribosome loading rates are counterbalanced by coordinated unloading rates, creating a self-regulatory loop that, as demonstrated through biophysical modeling and experimental validation in diverse cellular contexts, directly couples ribosome dynamics to mRNA stability. We further uncover how mRNA structural motifs and m6A methylation fine-tune ribosome dynamics at the isoform level, simultaneously modulating protein output and transcript half-life. In macrophages, this dynamic control enables rapid immune responses by upregulating translation efficiency of pro-inflammatory genes. Remarkably, these principles extend to synthetic mRNAs, where machine learning-guided optimization of ribosome dynamics enhances protein production. Our work establishes ribosome density dynamics as a pervasive and tunable regulatory axis, with broad implications for adaptive immunity, RNA biology, and the design of therapeutic mRNAs.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte

DISEASE(S): Acute Leukemia

SUBMITTER: Baoqiang Chen

LAB HEAD: Yihan Lin

PROVIDER: PXD070845 | Pride | 2025-12-10

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	CBQ_20240418_L1_1.raw	Raw
	CBQ_20240418_L1_2.raw	Raw
	CBQ_20240418_L2_1.raw	Raw
	CBQ_20240418_L2_2.raw	Raw
	CBQ_20240418_L3_1.raw	Raw

Items per page:

1 - 5 of 29

Similar Datasets

Ribosome dynamics orchestrate mRNA stability and translation across natural and synthetic systems

Project description:The dynamic interplay between ribosomes and mRNAs plays a central role in gene expression regulation, balancing protein synthesis and mRNA stability. However, traditional methods capturing static ribosome occupancy fail to resolve the temporal dynamics governing these processes. Here, we introduce Temporal Ribosome Density Profiling (TRiP), which combines metabolic RNA labeling and polysome sequencing to map ribosome density dynamics across the mRNA lifespan. TRiP reveals a striking temporal symmetry conserved across cell types: gene-specific ribosome loading rates are counterbalanced by coordinated unloading rates, creating a self-regulatory loop that, as demonstrated through biophysical modeling and experimental validation in diverse cellular contexts, directly couples ribosome dynamics to mRNA stability. We further uncover how mRNA structural motifs and m6A methylation fine-tune ribosome dynamics at the isoform level, simultaneously modulating protein output and transcript half-life. In macrophages, this dynamic control enables rapid immune responses by upregulating translation efficiency of pro-inflammatory genes. Remarkably, these principles extend to synthetic mRNAs, where machine learning-guided optimization of ribosome dynamics enhances protein production. Our work establishes ribosome density dynamics as a pervasive and tunable regulatory axis, with broad implications for adaptive immunity, RNA biology, and the design of therapeutic mRNAs.

2025-12-10 | PXD070830 | Pride

2E7 Antigen Identification Using PhAbomics Technology

Project description:Antibody–drug conjugates (ADCs) require antibodies with both high specificity and efficient internalization—features often overlooked by conventional discovery pipelines that rely on preselected antigens and recombinant proteins. Here, we present an integrated phenotypic platform that combines target-unbiased live-cell biopanning with in situ chemical crosslinking and mass spectrometry to concurrently identify internalizing 49 antibodies and their membrane-bound cognate antigens in a physiologic context.

2025-11-20 | PXD065365 | Pride

Nascent Ribo-Seq measures ribosomal loading time and reveals kinetic impact on ribosome density

Project description:mRNAs are generally assumed to be loaded instantly with ribosomes upon entry into the cytoplasm. To measure ribosome density on nascent mRNA, we developed nascent Ribo-Seq (nRibo-Seq) by combining Ribo-Seq with progressive 4-thiouridine labelling. In mouse macrophages, we experimentally determined, for the first time, the lag between the appearance of nascent RNA and its association with ribosomes, which was calculated to be 20 - 22 min for bulk mRNA, and approximated the time it takes for mRNAs to be fully loaded with ribosomes to be 41 - 44 min. Notably, ribosomal loading time is adapted to gene function as rapid loading was observed with highly regulated genes. The lag and ribosomal loading time correlate positively with ORF size and mRNA half-life, and negatively with tRNA adaptation index. Similar results were obtained in mouse embryonic stem cells, where the lag in ribosome loading was even more pronounced with 35 - 38 min. We validated our measurements after stimulation of macrophages with lipopolysaccharide, where the lag between cytoplasmic and translated mRNA leads to uncoupling between input and ribosome-protected fragments. Uncoupling is stronger for mRNAs with long ORFs or half-lives, a finding we also confirmed at the level of protein production by nascent chain proteomics. As a consequence of the lag in ribosome loading, ribosome density measurements are distorted when performed under conditions where mRNA levels are far from steady state expression, and transcriptional changes affect ribosome density in a passive way. This study uncovers an unexpected and considerable lag in ribosome loading, and provides guidelines for the interpretation of Ribo-Seq data taking passive effects on ribosome density into account.

2021-06-22 | PXD026828 | Pride

Mapping the Interactome of KRAS and Its G12C/D/V Mutants by Integrating TurboID Proximity Labeling with Quantitative Proteomics

Project description:RAS is one of the most frequently mutated proto-oncogenes in human malignancies, with mutation sites and subtypes exhibiting tumor-type dependent distribution. Oncogenic RAS mutations will maintain continuously GTP-bound activation states that leading to dysregulation of downstream signaling, ultimately disrupting cellular homeostasis to induce malignant transformation of cells. In this study, we employed TurboID proximity-labeling technology integrated with quantitative proteomics LC-MS/MS to systematically characterize the proximal binding proteins of wild-type KRAS and three high-frequency oncogenic mutant subtypes G12C, G12D and G12V. Through comprehensive bioinformatic analysis of mutation-specific interaction networks and distinct metabolic pathways, we identified significant enrichment of mutant KRAS binding proteins in insulin signaling pathway, reactive oxygen species related pathways, glucose and lipid metabolism and so on. Metabolic reprogramming pathways in KRAS G12 mutations collectively fuel tumor proliferation and immune evasion. In addition, we also comparatively analyzed the proximal binding proteins similarity in three G12 mutants. Notably, we observed that the KRAS E3 ubiquitin ligase adaptor LZTR1 diminished binding with mutations, and the mTORC1 important regulatory protein LAMTOR1 was enhanced recruitment by mutations. This multi-dimensional profiling delineates a comprehensive mapping of KRAS WT and G12 mutant interactomes and unveils the metabolic reprogramming pathways associated with KRAS activating mutations. Our analysis result provides potential therapeutic targets for KRAS-driven tumorigenesis while establishing a mechanistic framework for developing KRAS mutation-specific therapeutic strategies.

2025-06-09 | PXD062101 | Pride

Proteomic and Phosphoproteomic Profiling of Heart in Pak2cko Mice Under Pressure Overload

Project description:This study employs a factorial design to delineate the combinatorial effects of cardiac-specific conditional gene knockout and pressure overload-induced cardiac hypertrophy via transverse aortic constriction (TAC). Four experimental cohorts were established: (1) conditional knockout mice subjected to TAC (CKO_TAC), (2) knockout controls with Sham surgery (CKO_Sham), (3) floxed control mice receiving TAC (ff_TAC), and (4) floxed Sham-operated controls (ff_Sham). Following a 5-week pressure overload (TAC), myocardial tissue underwent parallel proteomic and phosphoproteomic profiling using TMT-based quantitative mass spectrometry. This dual-omics approach specifically interrogates: (a) the intrinsic genetic perturbation effect (CKO_ Sham vs ff_ Sham), (b) the pure pressure overload response (ff_TAC vs ff_Sham), and critically, (c) the genotype-by-environment interaction through synergistic/antagonistic divergence between observed versus predicted additive effects in CKO_TAC relative to genetic and surgical controls. Phosphoproteomic data further resolve signaling pathway dynamics underlying phenotypic modulation.

2025-09-25 | PXD067213 | Pride

A Single-copy Knock In Translating Ribosome ImmunoPrecipitation (SKI TRIP) tool kit for tissue specific profiling of actively translated mRNAs in C. elegans.

Project description:Translating Ribosome Affinity Purification (TRAP) methods have emerged as a powerful approach to profile actively translated transcripts in specific cell and tissue types. Epitope tagged ribosomal subunits are expressed in defined cell populations and used to pull down ribosomes and their associated mRNAs, providing a snapshot of cell type-specific translation occurring in that space and time. Current TRAP toolkits available to the C. elegans community have been built using multi-copy arrays, randomly integrated in the genome. Here we introduce a Single-copy Knock In Translating Ribosome ImmunoPrecipitation (SKI TRIP) tool kit, a collection of C. elegans strains engineered by CRISPR in which tissue specific expression of FLAG tagged ribosomal subunit protein RPL-22 is driven by cassettes present in single copy from defined sites in the genome. In depth characterization of the SKI TRIP strains and methodology shows that 3xFLAG tagged RPL-22 expressed from its endogenous locus or within defined cell types incorporates into actively translating ribosomes and can be used to efficiently and cleanly pull-down cell type specific transcripts without impacting overall mRNA translation or fitness of the animal. We propose SKI TRIP use for the study of processes that are acutely sensitive to changes in translation, such as aging.

2022-01-31 | GSE195601 | GEO

Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation

Project description:Microtubules play crucial roles in cellular architecture, intracellular transport, and mitosis. The availability of free tubulin subunits impacts polymerization dynamics and microtubule function. When cells sense excess free tubulin, they trigger degradation of the encoding mRNAs, which requires recognition of the nascent polypeptide by the tubulin-specific ribosome-binding factor TTC5. How TTC5 initiates decay of tubulin mRNAs is unknown. Here, our biochemical and structural analysis reveals that TTC5 recruits the poorly studied protein SCAPER to the ribosome. SCAPER in turn engages the CCR4-NOT deadenylase complex through its CNOT11 subunit to trigger tubulin mRNA decay. SCAPER mutants that cause intellectual disability and retinitis pigmentosa in humans are impaired in CCR4-NOT recruitment, tubulin mRNA degradation, and microtubule-dependent chromosome segregation. Our findings demonstrate how recognition of a nascent polypeptide on the ribosome is physically linked to mRNA decay factors via a relay of protein-protein interactions, providing a paradigm for specificity in cytoplasmic gene regulation.

2023-07-03 | PXD041096 | Pride

Sequence selectivity of macrolide-induced translational regulation

Project description:We sequenced a total of 12 cDNA libararies derived from fragmented total mRNA and ribosome protected mRNAs from azithromycin-treated and -untreated S. aureus samples. The data represented 2 independent biological replicates. Examination of the impact of azithromycin on global translatome, mRNA abundance and the ribosome density along the transcripts.

2014-11-03 | E-GEOD-57175 | biostudies-arrayexpress

Mathematical modeling of Trypanosoma brucei transcription

Project description:Trypanosome RNA polymerase II transcription is polycistronic, individual mRNAs being excised by trans splicing and polyadenylation. In this study, we refined the previously published mathematical model for bloodstream form parasites and extended it to the procyclic form. We used the model, together with known mRNA half-lives, to predict the abundances of individual mRNAs, assuming rapid, unregulated mRNA processing; then we compared the results with measured mRNA abundances. Remarkably, the abundances of most mRNAs in procyclic forms are predicted quite well by the model, being largely explained by variations in mRNA decay rates and length. In bloodstream forms substantially more mRNAs are less abundant than predicted. We list mRNAs that are likely to show particularly slow or inefficient processing, either in both forms or with developmental regulation. We also measured ribosome occupancies of all mRNAs in trypanosomes grown in the same conditions as were used to measure mRNA turnover. In procyclic forms there was a weak positive correlation between ribosome density and mRNA half-life, suggesting cross-talk between translation and mRNA decay; ribosome density was related to the proportion of the mRNA on polysomes, indicating control of translation initiation. Ribosomal protein mRNAs in procyclics appeared to be exceptionally rapidly processed but poorly translated. Through this study, we conclude that lLevels of mRNAs in procyclic form trypanosomes are determined mainly by length and mRNA decay, with some control of precursor processing. In bloodstream forms variations in nuclear events play a larger role in transcriptome regulation, suggesting acquisition of new control mechanisms during adaptation to mammalian parasitism. Ribosome profiling and mRNA libraries were constructed in triplicate from in vitro PCF and in duplicate from in vitro T. brucei Lister427, to understand global differntial gene transcription.

2016-03-16 | E-GEOD-79208 | biostudies-arrayexpress

Molecular basis of mRNA delivery to the bacterial ribosome by bS1 protein and RNA polymerase

Project description:The initiation of translation begins with formation of a ribosome-mRNA complex. In bacteria, the 30S ribosomal subunit is recruited to many mRNAs through both base pairing with the Shine Dalgarno (SD) sequence and RNA-binding by ribosomal protein bS1. Translation can initiate on mRNAs that are being transcribed, and RNA polymerase (RNAP) can promote recruitment of the pioneering 30S. Here we have examined ribosome recruitment to mRNAs using cryogenic electron microscopy (cryo-EM), single-molecule fluorescence co-localization, and whole-cell cross-linking mass spectrometry. Structures of 30S-mRNA complexes show that bS1 delivers the mRNA to the ribosome for SD duplex formation and initial 30S subunit activation. RNAP associates flexibly with the 30S platform during nascent mRNA delivery and accelerates their association in a bS1-dependent manner in vitro. Collectively, our data provide a mechanistic framework for how the SD duplex, ribosomal proteins and RNAP cooperate in 30S recruitment to mRNAs and thereby establish transcription-translation coupling.

2024-11-15 | PXD048229 | JPOST Repository

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