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Status |
Public on Jun 01, 2020 |
Title |
RNA metabolic rates profiling in Fragile X neurons |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Fragile X syndrome (FXS) is caused by inactivation of FMR1 gene and loss of its encoded product the RNA binding protein FMRP, which generally represses translation of its target transcripts in the brain. In mouse models of FXS (i.e., Fmr1 knockout animals; Fmr1 KO), deletion of Cpeb1, which encodes a translational activator, mitigates nearly all pathophysiologies associated with the disorder. We have observed that the wide-spread dys-regulation of RNA abundance in Fmr1 KO brain cortex and its rescue to normal levels in Fmr1/Cpeb1 double KO mice were the driver of the observed dys-regulation and rescue of translation as measured by whole transcriptome ribosome occupany in the brain. We hypothesize that in Fragile X brain there is wide spread dys-regulation at RNA stability level. Here we test this hypothesis by profiling RNA synthesis, processing and degradation rates in Fragile X and wild type neurons, by taking advantage of short 5-EU labeling and computational modeling. We show that, while RNA synthesis and processing rates were barely changed, there is wide-spread evelated RNA degradation rates in the Fragile X neurons, particularly for genes using optimal codons.
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Overall design |
RNA metabolic labeling coupled to RNA-seq in Fmr1-KO and wild type mouse neurons
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Contributor(s) |
Shu HR, Donnard E, Liu B, Richter JD |
Citation missing |
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Submission date |
Nov 19, 2019 |
Last update date |
Jun 01, 2020 |
Contact name |
Huan Raya Shu |
E-mail(s) |
dr.huan.shu@gmail.com
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Organization name |
University of Massachusetts Medical School
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Department |
Program in Molecular Medicine
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Lab |
Richter Lab
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Street address |
373 Plantation St
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City |
Worcester |
State/province |
MA |
ZIP/Postal code |
01605 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (10)
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Relations |
BioProject |
PRJNA590361 |
SRA |
SRP230603 |