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| Status |
Public on Sep 10, 2020 |
| Title |
Astroglial FMRP deficiency cell-autonomously up-regulates miR-128 and disrupts developmental astroglial mGluR5 signaling (miRNA) |
| Platform organism |
synthetic construct |
| Sample organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
The loss of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common inherited intellectual disability. How the loss of FMRP alters protein expression and astroglial functions remains essentially unknown. Here we showed that selective loss of astroglial FMRP in vivo up-regulates a brain-enriched miRNA, miR-128-3p, in mouse and human FMRP-deficient astroglia, which suppresses developmental expression of astroglial metabotropic glutamate receptor 5 (mGluR5), a major receptor in mediating developmental astroglia to neuron communication. Selective in vivo inhibition of miR-128-3p in FMRP-deficient astroglia sufficiently rescues decreased mGluR5 function, while astroglial overexpression of miR-128-3p strongly and selectively diminishes developmental astroglial mGluR5 signaling. Subsequent transcriptome and proteome profiling further suggests that FMRP commonly and preferentially regulates protein expression through posttranscriptional, but not transcriptional, mechanisms in astroglia. Overall, our study defines an FMRP-dependent cell-autonomous miR pathway that selectively alters developmental astroglial mGluR5 signaling, unveiling astroglial molecular mechanisms involved in FXS pathogenesis.
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| Overall design |
miRNA expression was profiled in cortical astroglia of Fmr1+/y and Fmr1−/y mice.
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| Contributor(s) |
Men Y, Yang Y |
| Citation missing |
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| |
| Submission date |
Sep 09, 2020 |
| Last update date |
Sep 14, 2020 |
| Contact name |
Yongjie Yang |
| E-mail(s) |
[email protected]
|
| Phone |
6176363643
|
| Organization name |
Tufts University School of Medicine
|
| Street address |
136 Harrison Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02111 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21572 |
[miRNA-4] Affymetrix Multispecies miRNA-4 Array [ProbeSet ID version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA662569 |
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