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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 09, 2021 |
| Title |
A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
In ribosomopathies, perturbed expression of ribosome components leads to tissue-specific phenotypes. What accounts for such tissue-selective manifestations as a result of mutations in the ribosome, a ubiquitous cellular machine, has remained a mystery. Combining mouse genetics and in vivo ribosome profiling, we observe limb patterning phenotypes in ribosomal protein (RP) haploinsufficient embryos and uncover selective translational changes of transcripts controlling limb development. Surprisingly, both loss of p53, which is activated by RP haploinsufficiency, and augmented protein synthesis rescue these phenotypes. These findings are explained by the identification that p53 functions as a master regulator of protein synthesis, at least in part, through transcriptional activation of 4E-BP1. 4E-BP1, a key translational regulator, in turn, facilitates selective changes in the translatome downstream of p53, and thereby explains how RP haploinsufficiency may elicit specificity to gene expression. These results provide an integrative model to understand how in vivo tissue-specific phenotypes emerge in ribosomopathies.
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| Overall design |
Ribosome profiling from E10.5 mouse forelimbs (N=3 of each genotype): Rps6lox/+;Trp53+/+, Prx1Cre;Rps6lox/+;Trp53+/+, Rps6lox/+;Trp53-/-, Prx1Cre;Rps6lox/+;Trp53-/-
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| Contributor(s) |
Tiu GC, Kerr CH, Forester CM, Krishnarao PS, Rosenblatt HD, Raj N, Lantz TC, Zhulyn O, Bowen ME, Shokat L, Attardi LD, Ruggero D, Barna M |
| Citation(s) |
34242585 |
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| Submission date |
Aug 12, 2019 |
| Last update date |
Aug 08, 2021 |
| Contact name |
Gerald Tiu |
| Organization name |
Stanford University
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| Street address |
279 Campus Dr., Beckman Center B309
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| City |
Stanford |
| State/province |
California |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA559859 |
| SRA |
SRP218125 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE135722_ribo_cds_rna_total_counts.csv.gz |
730.5 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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