A Rapid Translational Immune Response Program in CD8 Memory T Lymphocytes
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ABSTRACT:
PROVIDER: PRJNA707537 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13890644_1.fastq.gz | Fastqsanger.gz | |||
| SRR13890644_2.fastq.gz | Fastqsanger.gz | |||
| SRR13890645_1.fastq.gz | Fastqsanger.gz | |||
| SRR13890645_2.fastq.gz | Fastqsanger.gz | |||
| SRR13890646_1.fastq.gz | Fastqsanger.gz |
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Project description:Abstract: Immune cell activation is a very rapid and concerted cellular response that requires coordination between cellular processes that occur in different compartments and on very different time scales. Here, we use ribosome profiling and deep RNA sequencing to define the acute mRNA translation changes that follow initial signaling events and enable subsequent events of T cell activation and expansion. Briefly, early events in the activation of antigen experienced CD 8 T cells are insensitive to transcriptional blockade with actinomycin, and instead depend on the translation of pre-existing mRNAs and blocked by cycloheximide. Ribosome profiling identifies ~92 mRNAs that are recruited into ribosomes following CD8 T cell stimulation. These mRNAs typically have structured GC and pyrimidine rich 5’UTRs and they encode key regulators of T cell activation and proliferation such as Notch1, Ifngr1, Il2rb, serine metabolism enzymes Psat1 and Shmt2, and translation factors eEF1a1 and eEF2. The increased production of receptors of IL2 and IFNγ precedes the activation of gene expression and augments cellular signals and T cell activation. Together, we identify the early RNA translation program that acts in a feed-forward manner to enable the rapid and dramatic process of CD8 T cell expansion and activation.
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Project description:The activation of memory T cells is a very rapid and concerted cellular response that requires coordination between cellular processes in different compartments and on different time scales. In this study, we use ribosome profiling and deep RNA sequencing to define the acute mRNA translation changes in CD8 memory T cells following initial activation events. We find that initial translation enables subsequent events of human and mouse T cell activation and expansion. Briefly, early events in the activation of Ag-experienced CD8 T cells are insensitive to transcriptional blockade with actinomycin D, and instead depend on the translation of pre-existing mRNAs and are blocked by cycloheximide. Ribosome profiling identifies ∼92 mRNAs that are recruited into ribosomes following CD8 T cell stimulation. These mRNAs typically have structured GC and pyrimidine-rich 5' untranslated regions and they encode key regulators of T cell activation and proliferation such as Notch1, Ifngr1, Il2rb, and serine metabolism enzymes Psat1 and Shmt2 (serine hydroxymethyltransferase 2), as well as translation factors eEF1a1 (eukaryotic elongation factor α1) and eEF2 (eukaryotic elongation factor 2). The increased production of receptors of IL-2 and IFN-γ precedes the activation of gene expression and augments cellular signals and T cell activation. Taken together, we identify an early RNA translation program that acts in a feed-forward manner to enable the rapid and dramatic process of CD8 memory T cell expansion and activation.
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