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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 13, 2012 |
| Title |
FMR1 targets distinct mRNA sequence elements to regulate protein expression [Affymetrix] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMR1 (or FMRP). We report the discovery of the RNA recognition elements (RREs), binding sites, and mRNA targets for wild-type and I304N mutant FMRP isoforms as well as its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP can affect their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide an invaluable molecular guide towards the pursuit of novel therapeutic targets for these devastating neurological disorders.
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| Overall design |
The mRNA profile of RNA recovered from FLAG-antibody immunoprecipitated FMRP was compared to the mRNA profile of the starting lysate material.
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| Contributor(s) |
Ascano M, Mukherjee N, Bandaru P, Miller JB, Nusbam J, Corcoran D, Langlois C, Munschauer M, Hafner M, Williams Z, Ohler U, Tuschl T |
| Citation(s) |
23235829 |
| Submission date |
Jul 19, 2012 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Manuel Ascano, Jr. |
| Organization name |
The Rockefeller University
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| Department |
HHMI/Laboratory of RNA Molecular Biology
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| Lab |
Tuschl Laboratory
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| Street address |
1230 York Avenue Box 186
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021-6307 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE39686 |
FMR1 targets distinct mRNA sequence elements to regulate protein expression |
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| Relations |
| BioProject |
PRJNA170994 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE39504_RAW.tar |
18.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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