In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 53.19-53.19
Abstract:
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA. Recent conceptual and technological advances have sparked extensive research interests in the functional roles of m6A. The writers, erasers and readers of m6A have been identified and characterized in a number of biological processes in recent years. However, the physiological roles of m6A and its effectors in lymphogenesis remained unknown. Here, we report that loss of METTL14, a core component of the m6A writer complex, in mouse B lineage cells blocked B cell development. Deletion of METTL14 in developing B cells caused dramatic reductions in the mRNA m6A level, together with an incomplete blockage during the transition from the quiescent pro-B stage to the proliferating large pre-B stage as well as a complete blockage during the proliferation-to-quiescence transition between large pre-B and small pre-B stages. We found that & gt;67% transcripts contain m6A in developing B cells, suggesting that m6A might be widely involved in gene expression regulation. m6A controlled the quiescence-to-proliferation switch partially through its cytoplasmic reader YTHDF2, as deleting YTHDF2 partially mimicked the earlier incomplete blockage between pro-B and large pre-B stages due to METTL14 deficiency, but did not cause the later proliferation-to-quiescence blockage. Altogether, our data identifies m6A, which specifically controls transitions between quiescence and proliferation, as a critical new layer of gene expression regulation in B cell development.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.53.19
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
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