Molecular cell, 2021-10, Vol.81 (19), p.3949
2021
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- Autor(en) / Beteiligte
- Titel
- 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.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1097-4164DOI: 10.1016/j.molcel.2021.07.037Titel-ID: cdi_pubmed_primary_34450044
- Format
- –
- Schlagworte
- Adenosine - analogs & derivatives, Adenosine - metabolism, Animals, B-Lymphocytes - immunology, B-Lymphocytes - metabolism, Cytidine Deaminase - genetics, Cytidine Deaminase - metabolism, Exosome Multienzyme Ribonuclease Complex - genetics, Exosome Multienzyme Ribonuclease Complex - metabolism, Female, Genomic Instability, HEK293 Cells, Humans, Immunoglobulin Class Switching, Immunoglobulin Heavy Chains - genetics, Immunoglobulin Heavy Chains - metabolism, Male, Membrane Proteins - genetics, Membrane Proteins - metabolism, Methylation, Methyltransferases - genetics, Methyltransferases - metabolism, Mice, Mice, Knockout, Recombination, Genetic, RNA 3' End Processing, RNA, Long Noncoding - genetics, RNA, Long Noncoding - metabolism, RNA, Untranslated - genetics, RNA, Untranslated - metabolism