Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell size-dependent mRNA transcription drives proteome remodeling [SLAM-seq]

ABSTRACT: Increasing cell size drives proteomic changes that impact cell physiology. However, the molecular basis of size-dependent proteome remodeling has remained unclear. Here, we develop an inducible Cyclin D1 expression system in human cells to generate proliferating cells spanning over a two-fold size range. We use this system to make comprehensive genome-wide measurements of mRNA and protein concentrations and stability. We find that protein and mRNA turnover rates are weakly related to cell size, but that mRNA concentrations are strongly size-dependent. This establishes that transcriptional regulation is the basis of proteome remodeling. Live-cell imaging of nascent mRNAs using the MS2 system is used to measure how transcriptional dynamics change with cell size. Larger cells prolong transcriptional bursts and shorten inactive periods between bursts but maintain similar burst amplitudes to achieve transcriptional scaling. Together, our results show how transcription is modulated by cell size to remodel the proteome and alter cell physiology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE325723 | GEO | 2026/03/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE325723_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

Increasing cell size remodels the proteome and promotes senescence

Project description:Cell size is tightly controlled in healthy tissues, but it is unclear how deviations in cell size affect cell physiology. To address this, we measured how the proteome changes with cell size. Protein concentration changes are widespread and predicted by subcellular localization, size-dependent mRNA concentrations, and protein turnover. As proliferating cells grow larger, concentration changes associated with cellular senescence are increasingly pronounced, suggesting that large size may be a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative, DNA damage-, and CDK4/6i-induced senescence. Size-dependent changes to the proteome, including those associated with senescence, are not observed when an increase in cell size is accompanied by an increase in ploidy. Together, our findings show how cell size could impact many aspects of cell physiology through remodeling the proteome and provide a rationale for cell size control and polyploidization.

2022-08-01 | GSE208348 | GEO

Exploration and clinical validation of molecular typing of early colorectal cancer

Project description:Interventions: Case series:None Primary outcome(s): exon genes;transcriptional expression;proteome;protein phosphorylation group Study Design: Sequential

| 2739647 | ecrin-mdr-crc

RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size

Project description:A fundamental feature of cellular growth is that total protein and RNA amounts increase with cell size to keep concentrations approximately constant. A key component to this is that global transcription rates increase in larger cells. Here, we identify RNAPII as the limiting factor scaling mRNA transcription with cell size in budding yeast, as transcription is highly sensitive to the dosage of RNAPII but not to other components of the transcriptional machinery. Our experiments support a dynamic equilibrium model where global RNAPII transcription at a given size is set by the mass-action recruitment kinetics of unengaged nucleoplasmic RNAPII to the genome. However, this only drives a sub-linear increase in transcription with size, which is then partially compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to scale mRNA amounts with cell size.

2023-11-01 | GSE242874 | GEO

Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells

Project description:Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how cell size influences physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be compositionally different. Here, we utilize the natural heterogeneity of hepatocyte ploidy and yeast genetics to establish that ploidy-to-cell size ratio is a highly conserved determinant of proteome composition. In both mammalian and yeast cells, genome dilution by cell growth elicits a starvation-like phenotype, suggesting that growth in large cells is restricted by genome concentration in manner that mimics a limiting nutrient. Moreover, genome dilution explains some proteomic changes ascribed to yeast aging. Overall, our data indicate that genome concentration drives changes in cell composition independently of external environmental cues.

2024-06-05 | GSE269091 | GEO

Increasing cell size remodels the proteome and promotes senescence

Project description:Increasing cell size remodels the proteome and promotes senescence

| PRJNA859518 | ENA

Genome-wide interference of chromatin architecture and Mediator in transcriptional bursting and gene network regulation

Project description:Gene expression is a stochastic process that occurs in bursts of RNA synthesis. We applied a mathematical model to scRNA-Seq data to infer bursting dynamics transcriptome-wide under multiple perturbations in a wide range of cell types and identified possible molecular mechanisms. We find that mediator complex subunit MED26 primarily regulates frequency, MYC regulates burst size, while cohesin and super-enhancers can modulate both. Despite comparable effect sizes on RNA levels amongst these perturbations, we find that acute depletion of MED26 plays a larger role in perturbing gene regulatory networks. Furthermore, this perturbation acts downstream of both chromatin spatial architecture and preinitiation complex formation, indicating that later steps in the initiation of transcriptional bursts are primary nodes for integrating gene networks in single cells.

2024-06-30 | GSE241338 | GEO

Myc transcriptional bursts promote B cell positive selection by T cells in germinal centers

Project description:Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs) where B cells mutate their antibody-encoding genes in the dark zone (DZ) followed by a selection of the high-affinity variants in the light zone (LZ) by T cells. The amount of the T cell-derived selection signals is proportional to the BCR affinity and the magnitude of Myc expression. However, since the lifetimes of Myc mRNA and protein are extremely short, it is unclear how high levels of Myc are maintained in the GC B cell to allow positive selection. Here, by measuring Myc transcripts in situ at the single-cell level, we find that T cell help promotes the frequency of Myc transcriptional bursts. T cell help primarily increases the number of Myc-positive cells rather than the amount of Myc per cell. Measurement of Myc intronic and exonic transcripts in situ demonstrates that positive selection is mediated by Myc transcriptional bursts through a rapid increase in the active transcription sites rather than an elevation in transcription rate or gene accessibility. Thus, the amount of Myc transcriptional bursts over time in the LZ, rather than Myc abundance, dictates B cell selection in germinal centers.

2024-10-15 | GSE237128 | GEO

Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size

Project description:Biosynthesis scales with cell size such that protein concentrations generally remain constant as cells grow. As an exception, synthesis of the cell-cycle inhibitor Whi5 ‘sub-scales’ with cell size so that its concentration is lower in larger cells to promote cell-cycle entry. Here, we find that a transcriptional control uncouples Whi5 synthesis from cell size and, screening for similar genes, identify histones as the major class of sub-scaling transcripts besides WHI5. Histone synthesis is thereby matched to genome content rather than cell size. Such sub-scaling proteins are challenged by asymmetric cell division because proteins are typically partitioned in proportion to new-born cell volume. To avoid this fate, Whi5 uses chromatin-binding to partition similar protein amounts to each new-born cell regardless of cell size. Finally, disrupting both Whi5 synthesis and chromatin-based partitioning compromises G1 size control. Thus, specific transcriptional and partitioning mechanisms determine protein sub-scaling to control cell size.

2021-12-01 | GSE167842 | GEO

Myc transcriptional bursts promote B cell positive selection by T cells in germinal centers

Project description:Myc transcriptional bursts promote B cell positive selection by T cells in germinal centers

| PRJNA994027 | ENA

Single-cell response to LPS of wild-type and cohesin-deficient macrophages.

Project description:Transcription is an intermittent process that occurs in bursts. The frequency and the number of messenger RNA (mRNA) produced by these bursts determine expression levels and shape cell-to-cell variability. Productive encounters between enhancers and promoters control burst dynamics, which the cohesin complex can facilitate through loop extrusion. Cohesin is a ring-shaped complex involved in enhancer-promoter interactions. Without cohesin, bone-marrow-derived macrophages' transcriptional response to LPS is severely impaired (Cuartero et al., 2018). Single-cell RNA sequencing (scRNAseq) showed that the frequency of cells expressing inducible transcripts (as defined in Bhatt et al., 2012) was reduced in cohesion-deficient macrophages before and after LPS stimulation. In contrast, when considering only cells expressing LPS-inducible transcripts, cohesin-deficient macrophages showed reduced mean expression at baseline and late LPS-response (8h) but not in the early response (2h). These results support a model where cohesin is implicated in the control of burst frequencies upon LPS.

2022-04-17 | GSE190622 | 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