|
| Status |
Public on Jul 23, 2019 |
| Title |
RNA Seq of Fmr1 NPC nuclear fractions |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
N6-methyladenosine (m6A) modification of mRNA is emerging as a vital mechanism regulating RNA function. Here, we show that fragile X mental retardation protein (FMRP), an RNA-binding protein, reads m6A to regulate nuclear export of methylated mRNA targets during neural stem cell differentiation. In Fmr1 KO mice neural progenitors show delayed cell cycle exit and differentiation, resulting in their progressive accumulation in the ventricular and subventricular zones. RNA-seq of neural precursor cells (NPCs) from Fmr1 KO mice and m6A-seq uncovered nuclear retention of m6A-modified FMRP target mRNAs involved in regulating neural differentiation, including components of Notch and Hedgehog signaling pathways. Analysis of NPCs from Mettl14 cKO mice, which are devoid of m6A, revealed that methylation of RNAs promotes their nuclear export through CRM1. Altogether, our findings suggest that FMRP reads and facilitates nuclear export of m6A-modified mRNAs to regulate neural stem cell differentiation, contributing to Fragile X syndrome.
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| |
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| Overall design |
Comparison of nuclear RNAs from WT and Fmr1 KO NPCs from three independent lines
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| |
|
| Contributor(s) |
Ma YC |
| Citation missing |
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| |
| Submission date |
Oct 25, 2018 |
| Last update date |
Jul 24, 2019 |
| Contact name |
Brittany Megan Edens |
| Organization name |
Caltech
|
| Street address |
1200 E California Blvd
|
| City |
Pasadena |
| State/province |
CA |
| ZIP/Postal code |
91125 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA498497 |
| SRA |
SRP166885 |
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