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Mechanism of noncoding RNA-associated N 6 -methyladenosine recognition by an RNA processing complex during IgH DNA recombination
Ist Teil von
Molecular cell, 2021-10, Vol.81 (19), p.3949
Ort / Verlag
United States
Erscheinungsjahr
2021
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Immunoglobulin heavy chain (IgH) locus-associated G-rich long noncoding RNA (SμGLT) is important for physiological and pathological B cell DNA recombination. We demonstrate that the METTL3 enzyme-catalyzed N
-methyladenosine (m
A) RNA modification drives recognition and 3' end processing of SμGLT by the RNA exosome, promoting class switch recombination (CSR) and suppressing chromosomal translocations. The recognition is driven by interaction of the MPP6 adaptor protein with nuclear m
A reader YTHDC1. MPP6 and YTHDC1 promote CSR by recruiting AID and the RNA exosome to actively transcribe SμGLT. Direct suppression of m
A modification of SμGLT or of m
A reader YTHDC1 reduces CSR. Moreover, METTL3, an essential gene for B cell development in the bone marrow and germinal center, suppresses IgH-associated aberrant DNA breaks and prevents genomic instability. Taken together, we propose coordinated and central roles for MPP6, m
A modification, and m
A reader proteins in controlling long noncoding RNA processing, DNA recombination, and development in B cells.