Accession |
PRJCA001364 |
Title |
m6A methyltransferase METTL3 regulates TFH differentiation by modulating Tcf7 mRNA stability |
Relevance |
Medical |
Data types |
Raw sequence reads
|
Organisms |
Mus musculus
|
Description |
As a predominant mRNA modification in eukaryotes, N6-methyladenosine (m6A) has been documented essential functions at post-transcriptional regulation of mRNAs. Emerging evidences have revealed the importance of m6A in cell development and fate determination. However, its roles in adaptive immune cells remain largely unclear. Here, we report critical requirement of m6A in differentiation and function of follicular helper T cells (TFH cells). Conditional deletion of m6A methyltransferase METTL3 in CD4+ T cells remarkably impaired the initiation of TFH differentiation response against LCMV infection. Our data indicated that ablation of METTL3 led to low level of Tcf7 mRNA in TFH cells associated with reduced expression of its protein product TCF-1, which is an essential regulator for early TFH commitment. Further, forced expression of TCF-1 in METTL3-deficient CD4+ T cells could restore defective TFH differentiation. Mechanistically, METTL3 directed m6A modification in 3' UTR of Tcf7 and prevented its decay. Together, our findings uncover m6A serves as a modulator of TFH differentiation by controlling the stability of Tcf7 mRNA. |
Sample scope |
Multiisolate |
Release date |
2021-05-09 |
Grants |
Agency |
program |
Grant ID |
Grant title |
National Natural Science Foundation of China (NSFC)
|
|
31571522
|
|
National Natural Science Foundation of China (NSFC)
|
|
31630038
|
|
National Natural Science Foundation of China (NSFC)
|
|
31422037
|
|
National Natural Science Foundation of China (NSFC)
|
|
31825011
|
|
Ministry of Science and Technology of the People's Republic of China (MOST)
|
National Key Research and Development Program of China
|
2017YFA0104401
|
|
|
Submitter |
Yichang
Zhang (zhangyichang@big.ac.cn)
|
Organization |
Beijing Institute of Genomics, Chinese Academy of Sciences |
Submission date |
2019-04-08 |