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| Status |
Public on Nov 08, 2021 |
| Title |
TTP protects against acute liver failure by regulating CCL2 and CCL5 through m6A RNA methylation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tristetraprolin (TTP), an important immunosuppressive protein regulating mRNA decay through recognizing the AU-rich elements (AREs) within the 3’UTRs of mRNAs, participates in the pathogenesis of liver diseases. However, whether TTP regulates mRNA stability through other mechanisms remains poorly understood. Here, we report that TTP is upregulated in acute liver failure (ALF), resulting in decreased mRNA stabilities of C-C Motif Chemokine Ligand 2 (CCL2) and C-C Motif Chemokine Ligand 5 (CCL5) through promoting N6-methyladenosine (m6A) mRNA methylation. Overexpression of TTP can markedly ameliorate hepatic injury in vivo. TTP regulates the mRNA stabilization of CCL2 and CCL5. Interestingly, increased m6A methylation in CCL2 and CCL5 mRNAs promotes TTP-mediated RNA destabilization. Moreover, induction of TTP upregulates expression levels of WT1 associated protein (WTAP), Methyltransferase like 14 (METTL14), and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), which encode enzymes regulating m6A methylation, resulting in a global increase of m6A methylation and amelioration of live injury due to enhanced degradation of CCL2 and CCL5. These findings suggest a novel mechanism by which TTP modulates mRNA stabilities of CCL2 and CCL5 through m6A RNA methylation, which is involved in the pathogenesis of ALF.
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| Overall design |
RNA-Seq was performed in TTP stablely knockdown HL7702 cells.
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| Web link |
https://doi.org/10.1172/jci.insight.149276.
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| Contributor(s) |
Zhou R, Xiao P, Li M |
| Citation(s) |
34877932 |
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| Submission date |
Sep 07, 2020 |
| Last update date |
Feb 01, 2024 |
| Contact name |
RUI Zhou |
| E-mail(s) |
[email protected]
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| Organization name |
Wuhan University
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| Street address |
Donghu Road 185
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| City |
Wuhan |
| ZIP/Postal code |
430071 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA662043 |
| SRA |
SRP280344 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE157581_counts.txt.gz |
443.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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