| 项目编号 |
PRJCA022405 |
| 项目标题 |
METTL1-mediated tRNA m7G modification determines B cell responses in systemic autoimmunity |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
Single cell sequencing
ribo-seq
|
| 物种名称 |
Mus musculus
Homo sapiens
|
| 描述信息 |
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. |
| 样品范围 |
Single cell |
| 发布日期 |
2024-10-25 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 39638793
|
Aberrant METTL1-mediated tRNA m7G modification alters B-cell responses in systemic autoimmunity in humans and mice
|
Nature Communications
|
10.1038/s41467-024-54941-4
|
2024
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| 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
|
|
|
|
| 提交者 |
Hui
Zhang (zhangh656@mail.sysu.edu.cn)
|
| 提交单位 |
The First Affiliated Hospital, Sun Yat-sen University |
| 提交日期 |
2023-12-26 |
