Hien et al. 2020 (PRJNA666888)
General Details
| Title | Ribosome profiling and RNA-seq of wild-type hippocampal slices |
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| Organism | |
| Number of Samples | 10 |
| Release Date | 2020/10/01 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP286016 |
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| ENA | SRP286016 |
| GEO | GSE158881 |
| BioProject | PRJNA666888 |
Publication
| Title | |
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| Authors | Hien A, Molinaro G, Liu B, Huber KM, Richter JD |
| Journal | Molecular autism |
| Publication Date | 2020 Oct 14 |
| Abstract | Mutations in TSC2 are the most common cause of tuberous sclerosis (TSC), a disorder with a high incidence of autism and intellectual disability. TSC2 regulates mRNA translation required for group 1 metabotropic glutamate receptor-dependent synaptic long-term depression (mGluR-LTD) and behavior, but the identity of mRNAs responsive to mGluR-LTD signaling is largely unknown. We utilized Tsc2 +/- mice as a mouse model of TSC and prepared hippocampal slices from these animals. We induced mGluR-LTD synaptic plasticity in slices and processed the samples for RNA-seq and ribosome profiling to identify differentially expressed genes in Tsc2 +/- and following mGluR-LTD synaptic plasticity. Ribosome profiling reveals that in Tsc2 +/- mouse hippocampal slices, the expression of several mRNAs was dysregulated: terminal oligopyrimidine (TOP)-containing mRNAs decreased, while FMRP-binding targets increased. Remarkably, we observed the opposite changes of FMRP binding targets in Fmr1 -/y hippocampi. In wild-type hippocampus, induction of mGluR-LTD caused rapid changes in the steady-state levels of hundreds of mRNAs, many of which are FMRP targets. Moreover, mGluR-LTD failed to promote phosphorylation of eukaryotic elongation factor 2 (eEF2) in TSC mice, and chemically mimicking phospho-eEF2 with low cycloheximide enhances mGluR-LTD in TSC mice. These results suggest a molecular basis for bidirectional regulation of synaptic plasticity and behavior by TSC2 and FMRP. Our study also suggests that altered mGluR-regulated translation elongation contributes to impaired synaptic plasticity in Tsc2 +/- mice. |
| PMC | PMC7556950 |
| PMID | 33054857 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR12758951 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide |  |
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| SRR12758952 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758953 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758954 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758955 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758956 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758957 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758958 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758959 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| SRR12758960 | PRJNA666888 | Mus musculus | 0.0 | Ribo-Seq | Cycloheximide | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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