Coordination of protein synthesis and decay in mammalian cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE278929 | GEO | 2025/10/07
REPOSITORIES: GEO
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Project description:Protein synthesis and decay rates must be tightly coordinated to ensure proteome homeostasis. How this coordination is established is unknown. Here we use quantitative live cell imaging combined with computational inference and proteomics to determine how changes in global protein synthesis rates alter protein decay rates. A passive adaptation of protein degradation and dilution rates operates in cells tightly coupling proliferation rate to protein synthesis rates, allowing to partially buffer changes in proteome concentrations with increased loss of short-lived proteins. In contrast, the proliferation rate of mouse embryonic stem cells (mESCs) is hyposensitive to moderate changes in protein synthesis. mESCs uncouple protein degradation and dilution rates and robustly maintain their protein levels. Finally, we also show that differentiated human astrocytes strongly adapt protein degradation rates to altered protein synthesis. Our work illuminates the complex interplay between protein synthesis, degradation, and cell division to regulate proteome homeostasis.
2025-10-07 | PXD056601 | Pride
Project description:Steady-state RNA levels are a result of RNA synthesis and degradation. The importance of transcription-factor mediated induction or repression of mRNA synthesis is well established, but the role and mechanisms of RNA degradation are less well understood. We globally evaluated the RNA decay rates in proliferating and differentiated mouse myoblasts on whole-genome Affymetrix exon arrays, allowing for the assessment of directionality of RNA degradation and the detection of splice variant-specific differences in RNA decay rates. We found large differences in decay rates. mRNAs coding for proteins involved in signal transduction and transcriptional regulation have shortest half lives, whereas mRNAs coding for DNA replication enzymes and muscle contraction proteins are among the most stable. Many genes differentially expressed between proliferating and differentiated myoblasts demonstrate major differences in RNA decay rates. Quantitative PCR experiments confirmed the higher stability of transcripts with increased expression levels. RNA degradation has no apparent preferential directionality. RNA degradation appears to affect the ratio of different splice variants. For example, Itga7 isoforms with higher abundance in differentiated than in proliferating cells are more stable in differentiated cells, despite the sharing of a common 3’ untranslated region. Thus, where it was previously thought that the abundance of different splice isoforms was mainly controlled by tissue-specific splicing factors, we now demonstrate that isoforms may be produced at comparable levels but degraded with different efficiencies, depending on the differentiation status of the cells. Our results indicate that control of RNA degradation rates contributes significantly to the differentiation stage-dependent differences in abundance of transcripts and splice variants. Keywords: total RNA expression profiling; cultured cells We analyzed proliferating C2C12 cells and C2C12 cells differentiated into myotubes by serum starvation (8 days after induction of differentiation). We analyzed 7 time points after addition of actionmycin D (0, 10, 20, 30, 60, 150, 480 minutes). There were two biological replicates per condition.
2010-09-22 | E-GEOD-14387 | biostudies-arrayexpress
Project description:Steady-state RNA levels are a result of RNA synthesis and degradation. The importance of transcription-factor mediated induction or repression of mRNA synthesis is well established, but the role and mechanisms of RNA degradation are less well understood. We globally evaluated the RNA decay rates in proliferating and differentiated mouse myoblasts on whole-genome Affymetrix exon arrays, allowing for the assessment of directionality of RNA degradation and the detection of splice variant-specific differences in RNA decay rates. We found large differences in decay rates. mRNAs coding for proteins involved in signal transduction and transcriptional regulation have shortest half lives, whereas mRNAs coding for DNA replication enzymes and muscle contraction proteins are among the most stable. Many genes differentially expressed between proliferating and differentiated myoblasts demonstrate major differences in RNA decay rates. Quantitative PCR experiments confirmed the higher stability of transcripts with increased expression levels. RNA degradation has no apparent preferential directionality. RNA degradation appears to affect the ratio of different splice variants. For example, Itga7 isoforms with higher abundance in differentiated than in proliferating cells are more stable in differentiated cells, despite the sharing of a common 3’ untranslated region. Thus, where it was previously thought that the abundance of different splice isoforms was mainly controlled by tissue-specific splicing factors, we now demonstrate that isoforms may be produced at comparable levels but degraded with different efficiencies, depending on the differentiation status of the cells. Our results indicate that control of RNA degradation rates contributes significantly to the differentiation stage-dependent differences in abundance of transcripts and splice variants. Keywords: total RNA expression profiling; cultured cells
2010-09-22 | GSE14387 | GEO
Project description:The interplay between RNA transcription and degradation tightly regulates the dynamic changes of RNA abundance. To unveil the underlying regulatory mechanism of RNA in shaping gene expression patterns, it is essential yet challenging to profile the coordinated regulation of RNA synthesis and degradation rates at the single-cell level during dynamic programs such as cell differentiation and cell state transition. Herein, we propose scDUAL-seq, a double metabolic RNA labeling-based single-cell RNA sequencing method to simultaneously measure RNA synthesis and degradation rates in thousands of single cells during dynamic processes. In a cortisol response model of colorectal cancer cells, scDUAL-seq identifies the RNA regulatory strategies for 5,930 genes, discovers key regulons driving the strategy transitions, and disentangles the interplay between RNA synthesis and degradation that control distinct strategy transitions during cortisol response. We anticipate that scDUAL-seq will be broadly applied to record RNA kinetic rates and the underlying regulatory mechanism in diverse dynamic processes.
2025-07-01 | GSE286521 | GEO
Project description:T cells, crucial for immune regulation, risk malfunction leading to immune deficiencies or autoimmune diseases. Understanding the molecular cycle of T cell activation is vital for potential therapeutic interventions. Activation remodels the cellular transcriptome and proteome, impacting metabolism and protein synthesis pathways. The human genome encodes microRNAs (miRNAs), regulating hundreds of protein-coding mRNAs through translational repression and mRNA decay. While mRNA degradation is terminal, translational repression is reversible, allowing rapid responses to internal or external cues. In this study, we investigated changes in the miRNA repertoire and their impact on translational repression and mRNA degradation during T cell activation using high-throughput techniques. Our findings reveal that miRNAs induced upon T cell activation clear their targets through multiple pathways, with some following the canonical path of mRNA degradation and others initiating translational repression before mRNA degradation.
2025-08-08 | GSE254230 | GEO
Project description:T cells, crucial for immune regulation, risk malfunction leading to immune deficiencies or autoimmune diseases. Understanding the molecular cycle of T cell activation is vital for potential therapeutic interventions. Activation remodels the cellular transcriptome and proteome, impacting metabolism and protein synthesis pathways. The human genome encodes microRNAs (miRNAs), regulating hundreds of protein-coding mRNAs through translational repression and mRNA decay. While mRNA degradation is terminal, translational repression is reversible, allowing rapid responses to internal or external cues. In this study, we investigated changes in the miRNA repertoire and their impact on translational repression and mRNA degradation during T cell activation using high-throughput techniques. Our findings reveal that miRNAs induced upon T cell activation clear their targets through multiple pathways, with some following the canonical path of mRNA degradation and others initiating translational repression before mRNA degradation.
2025-08-08 | GSE254220 | GEO
Project description:T cells, crucial for immune regulation, risk malfunction leading to immune deficiencies or autoimmune diseases. Understanding the molecular cycle of T cell activation is vital for potential therapeutic interventions. Activation remodels the cellular transcriptome and proteome, impacting metabolism and protein synthesis pathways. The human genome encodes microRNAs (miRNAs), regulating hundreds of protein-coding mRNAs through translational repression and mRNA decay. While mRNA degradation is terminal, translational repression is reversible, allowing rapid responses to internal or external cues. In this study, we investigated changes in the miRNA repertoire and their impact on translational repression and mRNA degradation during T cell activation using high-throughput techniques. Our findings reveal that miRNAs induced upon T cell activation clear their targets through multiple pathways, with some following the canonical path of mRNA degradation and others initiating translational repression before mRNA degradation.
2025-08-08 | GSE254157 | GEO
Project description:In order to characterize plant protein degradation rates and understand their determinants as they relate to plant growth rate, we have applied 15N labelling approaches in leaves of the Arabidopsis rosette. We found a series of leaves in Arabidopsis plants for which the proteome was stable over time and degradation rates of individual proteins could thus be measured by considering the dilution of total protein abundance through growth. By progressively labelling new peptides with 15N and measuring the decrease in the abundance of over 60,000 peptides with natural isotope abundance profiles we determined the degradation rate of 1228 proteins. The exponential constant of the decay rate (KD) for each protein calculated from the relative isotope abundance of each peptide and the fold change in protein abundance during growth showed a wide distribution, ranging from 0 to 2 per day. This showed Arabidopsis protein half-lives vary from several hours to several months. In assessing intrinsic factors to explain these protein degradation rates, little effect of the N-end amino acid of proteins or of protein aggregation propensity were found, however protein complex membership and specific protein domains were strong predictors of degradation rate. We found new rapidly degrading subunits in a variety of protein complexes in plastids, identified the set of plant proteins whose degradation rate changes in different leaves of the rosette and correlated with leaf growth rate, and calculated the protein turnover energy costs in different leaves and their key determinants within the proteome.
2017-02-01 | PXD004550 | Pride
Project description:In order to characterize plant protein degradation rates and understand their determinants as they relate to plant growth rate, we have applied 15N labelling approaches in leaves of the Arabidopsis rosette. We found a series of leaves in Arabidopsis plants for which the proteome was stable over time and degradation rates of individual proteins could thus be measured by considering the dilution of total protein abundance through growth. By progressively labelling new peptides with 15N and measuring the decrease in the abundance of over 60,000 peptides with natural isotope abundance profiles we determined the degradation rate of 1228 proteins. The exponential constant of the decay rate (KD) for each protein calculated from the relative isotope abundance of each peptide and the fold change in protein abundance during growth showed a wide distribution, ranging from 0 to 2 per day. This showed Arabidopsis protein half-lives vary from several hours to several months. In assessing intrinsic factors to explain these protein degradation rates, little effect of the N-end amino acid of proteins or of protein aggregation propensity were found, however protein complex membership and specific protein domains were strong predictors of degradation rate. We found new rapidly degrading subunits in a variety of protein complexes in plastids, identified the set of plant proteins whose degradation rate changes in different leaves of the rosette and correlated with leaf growth rate, and calculated the protein turnover energy costs in different leaves and their key determinants within the proteome.
2017-02-01 | PXD004549 | Pride
Project description:The goal of this study is to measure Arabidopsis mRNA transcription and mRNA decay rates genome wide at two temperatures, and thus to calculate the temperature coefficient of both processes. Sensing and response to ambient temperature is important for controlling growth and development of many organisms, in part by regulating mRNA levels. mRNA abundance can change with temperature, but it is unclear whether this results from changes to transcription or decay rates and whether passive or active temperature regulation is involved. Results Using a base analogue labelling method we directly measured the temperature coefficient (Q10) of mRNA synthesis and degradation rates of the Arabidopsis transcriptome. We show that for most genes transcript levels are buffered against passive increases in transcription rates by balancing passive increases in the rate of decay. Strikingly, for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay and not vice versa, suggesting a global transcriptional mechanism process exists for the activethat controls of mRNA abundance by temperature/
2013-12-07 | GSE53071 | GEO