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

Project Data

Resource name Description
BioSample (8)  show -
GSA (1) -
CRA001529 m6A methyltransferase METTL3 regulates TFH differentiation by modulating Tcf7 mRNA stability