 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 19, 2024 |
| Title |
Epitranscriptomic Reader YTHDF2 Regulates SEK1(MAP2K4)-JNK-cJUN Inflammatory Signaling in Astrocytes during Neurotoxic Stress |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
As the most abundant glial cells in the CNS, astrocytes dynamically respond to neurotoxic stress, however, the key molecular regulators controlling the inflammatory status of these sentinels during neurotoxic stress have remained elusive. Herein, we demonstrate that the m6A epitranscriptomic mRNA modification tightly regulates the pro-inflammatory functions of astrocytes. Specifically, the astrocytic neurotoxic stresser, manganese (Mn), downregulated the m6A reader YTHDF2 in human and mouse astrocyte cultures and in the mouse brain. Functionally, YTHDF2 knockdown augmented, while its overexpression dampened, neurotoxic stress induced proinflammatory response, suggesting YTHDF2 serves as a key upstream regulator of inflammatory responses in astrocytes. Mechnistically, YTHDF2 RIP-sequencing identified MAP2K4 (MKK4; SEK1) mRNA as a YTHDF2 target influencing inflammatory signaling. Our target validation revealed Mn-exposed astrocytes mediates proinflammatory response by activating the phosphorylation of SEK1, JNK, and cJUN signaling. Collectively, YTHDF2 serves a key upstream ‘molecular switch’ controlling SEK1(MAP2K4)-JNK-cJUN proinflammatory signaling in astrocytes.
|
| |
|
| Overall design |
Human U251-MG astrocytoma cells were treated with manganese chloride (100 µM) and YTHDF2-RIP sequencing was performed to identify YTHDF2 target mRNAs that may control astrocytic inflammation. We expected a loss of enrichment in manganese-treated samples, concurrent with an upregulation of its cognate protein. 3 samples per group (control vs manganese), both inputs and immunoprecipitated fractions.
|
| Web link |
https://doi.org/10.1101/2024.01.26.577106
|
| |
|
| Contributor(s) |
Malovic E, Ealy A, Hsu PJ, Sarkar S, Miller C, Rokad D, Goeser C, Hartman AK, Zhu A, Palanisamy B, Zenitsky G, Jin H, Anantharam V, Kanthasamy A, He C, Kanthasamy AG, Jan A |
| Citation(s) |
39252959 |
| |
| Submission date |
Jan 31, 2024 |
| Last update date |
Oct 09, 2024 |
| Contact name |
Anumantha G Kanthasamy |
| E-mail(s) |
anumantha.kanthasamy@uga.edu
|
| Organization name |
University of Georgia
|
| Street address |
B122 Life Sciences Bldg University of Georgia
|
| City |
Athens |
| State/province |
GA |
| ZIP/Postal code |
30602 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA1071575 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE254720_counts.rip1.xlsx |
2.3 Mb |
(ftp)(http) |
XLSX |
| GSE254720_exp.rip1.xlsx |
3.4 Mb |
(ftp)(http) |
XLSX |
| GSE254720_exp.rip1_analysis.xlsx |
12.5 Mb |
(ftp)(http) |
XLSX |
| GSE254720_isoCounts.rip1.xlsx |
8.7 Mb |
(ftp)(http) |
XLSX |
| GSE254720_summary.rip1.xlsx |
10.1 Kb |
(ftp)(http) |
XLSX |
| GSE254720_transcript.rip1.xlsx |
11.5 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...