First Author | Zheng Z | Year | 2020 |
Journal | Cell Rep | Volume | 31 |
Issue | 13 | Pages | 107819 |
PubMed ID | 32610122 | Mgi Jnum | J:299956 |
Mgi Id | MGI:6488959 | Doi | 10.1016/j.celrep.2020.107819 |
Citation | Zheng Z, et al. (2020) Control of Early B Cell Development by the RNA N(6)-Methyladenosine Methylation. Cell Rep 31(13):107819 |
abstractText | The RNA N(6)-methyladenosine (m(6)A) methylation is installed by the METTL3-METTL14 methyltransferase complex. This modification has critical regulatory roles in various biological processes. Here, we report that deletion of Mettl14 dramatically reduces mRNA m(6)A methylation in developing B cells and severely blocks B cell development in mice. Deletion of Mettl14 impairs interleukin-7 (IL-7)-induced pro-B cell proliferation and the large-pre-B-to-small-pre-B transition and causes dramatic abnormalities in gene expression programs important for B cell development. Suppression of a group of transcripts by cytoplasmic m(6)A reader YTHDF2 is critical to the IL-7-induced pro-B cell proliferation. In contrast, the block in the large-pre-B-to-small-pre-B transition is independent of YTHDF1 or YTHDF2 but is associated with a failure to properly upregulate key transcription factors regulating this transition. Our data highlight the important regulatory roles of the RNA m(6)A methylation and its reader proteins in early B cell development. |