Omics · study · 2026
METTL3-mediated m6A modification controls Tcra recombination center formation and thymic T cell development
Listed in NCBI GEO
N6-methyladenosine (m6A) is the most prevalent internal modification of RNA, and METTL3 functions as the catalytic core of the methyltransferase complex.
Description
While m6A regulates T cell activation and differentiation, whether this RNA modification participates in antigen receptor V(D)J recombination remains unknown. Using conditional Mettl3 knockout mice and multi-omic profiling, we examined m6A function in thymocyte development and Tcra rearrangement.
Mettl3 deficiency reduced thymic cellularity by about 20-30%, substantially decreased double-positive (DP) thymocytes, diminished peripheral CD8+ T cells, and selectively impaired Tcra but not Tcrb rearrangement. Mechanistically, m6A specifically decorated TEA germline transcripts and maintained recombination center architecture. METTL3 loss abolished m6A enrichment at TEA, diminished Eα-TEA chromatin looping, and reduced germline transcription.
Read the rest (1 more)
Concurrently, rearranged Tcra translation efficiency fell to about 40% of wild-type levels, significantly reducing TCR-CD3 surface expression on DP, CD4 SP, and CD8 SP cells. Mettl3 knockout further upregulated DNA repair genes such as Lig4, Fignl1, and Rad51ap1, activated the interferon pathway, and increased γH2A.X DNA double-strand break markers and double-stranded RNA accumulation in DP thymocytes. Collectively, these results establish RNA m6A modification as a previously unrecognized regulatory layer of V(D)J recombination that controls recombination center formation and preserves genomic integrity during Tcra gene rearrangement.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333480 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333480 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1471173 ncbi.nlm.nih.gov/bioproject/PRJNA1471173 ↗
project · from NCBI GEO
Topics
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE333480 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].geo_series_type:methylation-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |