Similar Datasets
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that link them are not fully understood. Here, we studied these mechanisms in embryonic stem cells (ESCs). Transcripts showed a wide range of stabilities, which correlated with their relative translation levels and that did not change during early ESC differentiation. The protein DHH1 links translation to mRNA stability in yeast; however, loss of the mammalian homolog, DDX6, in ESCs did not disrupt the correlation across transcripts. Instead, the loss of DDX6 led to upregulated translation of microRNA targets, without concurrent changes in mRNA stability. The Ddx6 knockout cells were phenotypically and molecularly similar to cells lacking all microRNAs (Dgcr8 knockout ESCs). These data show that the loss of DDX6 can separate the two canonical functions of microRNAs: translational repression and transcript destabilization. Furthermore, these data uncover a central role for translational repression independent of transcript destabilization in defining the downstream consequences of microRNA loss.
| S-EPMC6086665 | biostudies-literature
Project description:Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells
| PRJNA448913 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-08-08 | GSE254231 | GEO
Project description:Rett syndrome (RTT) is caused by mutations of MECP2, a methyl CpG binding protein thought to act as a global transcriptional repressor. Here we show, using an isogenic human embryonic stem cell model of RTT, that MECP2 mutant neurons display key molecular and cellular features of this disorder. Unbiased global gene expression analyses demonstrate that MECP2 functions as a global activator in neurons but not in neural precursors. Decreased transcription in neurons was coupled with a significant reduction in nascent protein synthesis and lack of MECP2 was manifested as a severe defect in the activity of the AKT/mTOR pathway. Lack of MECP2 also leads to impaired mitochondrial function in mutant neurons. Activation of AKT/mTOR signaling by exogenous growth factors or by depletion of PTEN boosted protein synthesis and ameliorated disease phenotypes in mutant neurons. Our findings indicate a vital function for MECP2 in maintaining active gene transcription in human neuronal cells.
| S-EPMC4053296 | biostudies-literature
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: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:Stress tolerance and rapid growth are often competing interests in cells. Upon severe environmental stress, many organisms activate defense systems concurrent with growth arrest. There has been debate as to whether aspects of the stress-activated transcriptome are regulated by stress or an indirect byproduct of reduced proliferation. For example, stressed Saccharomyces cerevisiae cells mount a common gene expression program called the environmental stress response (ESR) [1] comprised of ∼300 induced (iESR) transcripts involved in stress defense and ∼600 reduced (rESR) mRNAs encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RiBi) important for division. Because ESR activation also correlates with reduced growth rate in nutrient-restricted chemostats and prolonged G1 in slow-growing mutants, an alternate proposal is that the ESR is simply a consequence of reduced division [2-5]. A major challenge is that past studies did not separate effects of division arrest and stress defense; thus, the true responsiveness of the ESR-and the purpose of stress-dependent rESR repression in particular-remains unclear. Here, we decoupled cell division from the stress response by following transcriptome, proteome, and polysome changes in arrested cells responding to acute stress. We show that the ESR cannot be explained by changes in growth rate or cell-cycle phase during stress acclimation. Instead, failure to repress rESR transcripts reduces polysome association of induced transcripts, delaying production of their proteins. Our results suggest that stressed cells alleviate competition for translation factors by removing mRNAs and ribosomes from the translating pool, directing translational capacity toward induced transcripts to accelerate protein production.
| S-EPMC6132260 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-12-29 | GSE248729 | GEO
Project description:Cell fate determination in the early mammalian embryo is regulated by multiple mechanisms. Recently, genes involved in vesicular trafficking have been shown to play an important role in cell fate choice, although the regulation of their expression remains poorly understood. Here we demonstrate for the first time that multiple endocytosis associated genes (EAGs) are repressed through a novel, dual mechanism in mouse embryonic stem cells (mESCs). This involves the action of the Polycomb Repressive Complex, PRC2, as well as post-transcriptional regulation by the ESC-specific cell cycle-regulating (ESCC) family of microRNAs. This repression is relieved upon differentiation. Forced expression of EAGs in mESCs results in a decrease in pluripotency, highlighting the importance of dual repression in cell fate regulation. We propose that endocytosis is critical for cell fate choice, and dual repression may function to tightly regulate levels of endocytic genes.
| S-EPMC5730570 | biostudies-literature
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