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| Status |
Public on Mar 10, 2019 |
| Title |
Widespread Alterations in Translation Elongation in the Brain of Fmr1 Knock-Out Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
FMRP is a polysome-associated RNA-binding protein encoded by Fmr1 and lost in Fragile X syndrome. Increasing evidence suggests that FMRP regulates both translation initiation and elongation, but the gene-specificity of these effects is unclear. To elucidate the effects of FMRP loss on translation, we used ribosome profiling for genome-wide measurements of ribosomal occupancy and positioning in the cortex of Fmr1 knock-out mice. We found a remarkably coherent reduction in ribosome footprint abundance per mRNA for previously identified, high-affinity mRNA binding partners of FMRP, and an increase for terminal oligo-pyrimidine (TOP) motif-containing genes canonically controlled by mTOR-4EBP-eIF4E signaling. Amino acid motif- and gene-level analyses both showed a widespread reduction of translational pausing in Fmr1 knock-out mice. Our findings are consistent with a model of FMRP-mediated regulation of both translation initiation through eIF4E and elongation that is disrupted in Fragile X syndrome.
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| Overall design |
Examination of genome-wide translational state in Fmr1-deficient and wild-type mouse cortex via next-generation sequencing-based profiling of transcription and translation
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| Contributor(s) |
Sharma SD, Metz J, Li H, Hobson B, Hornstein N, Sulzer D, Tang G, Sims PA |
| Citation(s) |
30893603 |
| |
| Submission date |
May 04, 2018 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter Sims |
| E-mail(s) |
pas2182@cumc.columbia.edu
|
| Organization name |
Columbia University
|
| Department |
Systems Biology
|
| Street address |
3960 Broadway
|
| City |
New York |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA464051 |
| SRA |
SRP144655 |
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