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| Status |
Public on Mar 17, 2022 |
| Title |
Downregulation of m6A methyltransferase in the hippocampus of Tyrobp-/- mice and implications for learning and memory deficits |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Loss-of-function mutations in the gene that encodes TYRO protein kinase-binding protein (TYROBP) cause Nasu-Hakola disease, a heritable disease resembling Alzheimer's disease (AD). Methylation of N6 methyl-adenosine (m6A) in mRNA plays essential roles in learning and memory. Aberrant m6A methylation has been detected in AD patients and animal models. In the present study, Tyrobp−/− mice showed learning and memory deficits in the Morris water maze, which worsened with age. Tyrobp−/− mice also showed elevated levels of total tau, Ser202/Thr205-phosphorylated tau and amyloid β in the hippocampus and cerebrocortex, which worsened with aging. The m6A methyltransferase components METTL3, METTL14, and WTAP were downregulated in Tyrobp−/− mice, while expression of demethylases that remove the m6A modification (e.g., FTO and ALKBH5) were unaltered. Methylated RNA immunoprecipitation sequencing identified 498 m6A peaks that were upregulated in Tyrobp−/− mice, and 312 m6A peaks that were downregulated. Bioinformatic analysis suggested that most of these m6A peaks occur in sequences near stop codons and 3′-untranslated regions. These findings suggest an association between m6A RNA methylation and pathological TYROBP deficiency.
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| Overall design |
m6A methylation in six months old wild type and Tyrobp (-/-) mice
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| Contributor(s) |
Zhanyun L, Tongxiao X, Ran L, Dejie Z, Yanxin L, Wei L, Yan Y, Yanlei H |
| Citation(s) |
35386591 |
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| Submission date |
Jul 09, 2021 |
| Last update date |
Apr 19, 2022 |
| Contact name |
Zhanyun Lv |
| E-mail(s) |
0618511@zju.edu.cn
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| Phone |
13562742976
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| Organization name |
the Affiliated Hospital of Jining Medical University
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| Street address |
Guhuai Road
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| City |
Jining |
| State/province |
Shandong |
| ZIP/Postal code |
272000 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA745190 |
| SRA |
SRP327666 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE179827_Raw_counts.txt.gz |
483 b |
(ftp)(http) |
TXT |
| GSE179827_TYROBP_IP_VS_TYROBP_input_peak.txt.gz |
4.8 Mb |
(ftp)(http) |
TXT |
| GSE179827_TYROBP_VS_WT_diff_Peak_result.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE179827_WT_IP_VS_WT_input_peak.txt.gz |
4.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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