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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 09, 2018 |
| Title |
Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
N6-methyladenosine (m6A) is the most prevalent internal modification of mammalian messenger RNAs (mRNAs) and long non-coding RNAs. The biological functions of this reversible RNA modification can be interpreted by cytoplasmic and nuclear "m6A reader" proteins to fine-tune gene expression, such as mRNA degradation and translation initiation. Here we profiled transcriptome-wide m6A sites in adult mouse cerebral cortex, underscoring that m6A is a widespread epitranscriptomic modification in brain. Interestingly, the mRNA targets of fragile X mental retardation protein (FMRP), a selective RNA-binding protein, are enriched for m6A marks. Loss of functional FMRP leads to Fragile X syndrome (FXS), the most common inherited form of intellectual disability. Transcriptome-wide gene expression profiling identified 2,035 genes differentially expressed in the absence of FMRP in cortex, and 92.5% of 174 downregulated FMRP targets are marked by m6A. Biochemical analyses indicate that FMRP binds to the m6A sites of its mRNA targets and interacts with m6A reader YTHDF2 in an RNA-independent manner. FMRP maintains the stability of its mRNA targets while YTHDF2 promotes the degradation of these mRNAs. These data together suggest that FMRP regulates the stability of its m6A-marked mRNA targets through YTHDF2, which could potentially contribute to the molecular pathogenesis of FXS.
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| Overall design |
Gene expression analyses were performed on mRNA samples isolated from the cerebral cortex of 6-week-old wild-type and Fmr1 KO male mice. N6-methyladenosine (m6A) epitranscriptome profiling was performed on the same mRNA samples. Six mice were pooled for each biological repilcate.
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| Contributor(s) |
Zhang F, Jin P |
| Citation(s) |
30107516 |
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| Submission date |
Nov 28, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Feiran Zhang |
| Organization name |
Emory University
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| Department |
Human Genetics
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| Lab |
Peng Jin
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| Street address |
615 Michael St NE
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| GSM2866910 |
RNA-seq, 6-week-old WT mice, cerebral cortex, non-IP, replicate 1 |
| GSM2866911 |
RNA-seq, 6-week-old WT mice, cerebral cortex, m6A-IP, replicate 1 |
| GSM2866912 |
RNA-seq, 6-week-old WT mice, cerebral cortex, non-IP, replicate 2 |
| GSM2866913 |
RNA-seq, 6-week-old WT mice, cerebral cortex, m6A-IP, replicate 2 |
| GSM2866914 |
RNA-seq, 6-week-old Fmr1 KO mice, cerebral cortex, non-IP, replicate 1 |
| GSM2866915 |
RNA-seq, 6-week-old Fmr1 KO mice, cerebral cortex, m6A-IP, replicate 1 |
| GSM2866916 |
RNA-seq, 6-week-old Fmr1 KO mice, cerebral cortex, non-IP, replicate 2 |
| GSM2866917 |
RNA-seq, 6-week-old Fmr1 KO mice, cerebral cortex, m6A-IP, replicate 2 |
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| Relations |
| BioProject |
PRJNA420074 |
| SRA |
SRP125761 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107434_RAW.tar |
904.4 Mb |
(http)(custom) |
TAR (of FPKM_TRACKING, TDF, TXT) |
| GSE107434_RNASeq-Fmr1KO-mice-CTX-6week-m6AIP_MeTPeak.txt.gz |
311.0 Kb |
(ftp)(http) |
TXT |
| GSE107434_RNASeq-WT-mice-CTX-6week-m6AIP_MeTPeak.txt.gz |
189.9 Kb |
(ftp)(http) |
TXT |
| GSE107434_RNASeq-mice-CTX-6week-m6AIP_MeTDiff_KOvsWT_.txt.gz |
341.2 Kb |
(ftp)(http) |
TXT |
| GSE107434_RNASeq-mice-CTX-6week_cuffdiff_KOvsWT_genes.txt.gz |
651.2 Kb |
(ftp)(http) |
TXT |
| GSE107434_RNASeq-mice-CTX-6week_cuffdiff_KOvsWT_isoforms.txt.gz |
923.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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