Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [RIBOseq]
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ABSTRACT:
PROVIDER: PRJNA1069046 | ENA |
REPOSITORIES: ENA
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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.
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Project description:Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation
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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.
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Project description:Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [miRNA-Seq]
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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.
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
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Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
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Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
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