Accession PRJCA022405
Title METTL1-mediated tRNA m7G modification determines B cell responses in systemic autoimmunity
Relevance Medical
Data types Transcriptome or Gene expression
Single cell sequencing
ribo-seq
Organisms Mus musculus
Homo sapiens
Description Upon activation, B cells exit their quiescent state and enter germinal center responses with massive changes in translation. Here, we identify METTL1 as a translational checkpoint during B cell activation. Conditional knock out of METTL1 in B cells blocks GC entry and impairs GC formation, leading to accumulation of GC precursors. In contrast, conditional knock-in of METTL promotes GC responses. Mechanistically, METTL catalyzes mG modification on specific subset of transfer RNAs that leads to biased preferential translation in B cell receptor signaling pathway. BCR signaling promotes electron transporter chain activities to ensure sufficient bioenergy. Pathologically, METTL mediated tRNA mG modification promotes B cell differentiation in SLE and deletion of METTL alleviates auto-reactive B cell responses during autoimmune induction. Overall, our study uncovers the essential role of METTL for effective B cell responses and aberrant tRNA mG modification by METTL promotes auto-reactive B cells in systemic autoimmunity.
Sample scope Single cell
Release date 2024-10-25
Grants
Agency program Grant ID Grant title
National Natural Science Foundation of China (NSFC) General Program 82071819
National Natural Science Foundation of China (NSFC) General Program 81971519
National Natural Science Foundation of China (NSFC) General Program 82171770
Submitter Hui Zhang (zhangh656@mail.sysu.edu.cn)
Organization The First Affiliated Hospital, Sun Yat-sen University
Submission date 2023-12-26

Project Data

Resource name Description
BioSample (17)  show -
GSA (4) -
CRA014155 METTL1-mediated tRNA m7G modification determines B cell responses in systemic autoimmunity
CRA018131 TRAC-seq data of METTL1-mediated tRNA m7G modification determines B cell responses in systemic autoimmunity
CRA017868 bulk rna-seq data of METTL1-mediated tRNA m7G modification determines B cell responses in systemic autoimmunity
CRA014160 ribo-seq and rna-seq data of METTL1-mediated tRNA m7G modification determines B cell responses in systemic autoimmunity