Other
15 Authors
- Rothschild G,
- Basu U,
- Munteanu EL,
- Swayne T,
- Wu L,
- Alvarez NS,
- Ding L,
- Lim J,
- Lee H,
- Zhang W,
- Hanna JH,
- Jha MK,
- Liu ZP,
- Nair L,
- Laffleur B
| First Author | Nair L | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 19 | Pages | 3949-3964.e7 |
| PubMed ID | 34450044 | Mgi Jnum | J:315843 |
| Mgi Id | MGI:6831143 | Doi | 10.1016/j.molcel.2021.07.037 |
| Citation | Nair L, et al. (2021) Mechanism of noncoding RNA-associated N(6)-methyladenosine recognition by an RNA processing complex during IgH DNA recombination. Mol Cell 81(19):3949-3964.e7 |
| abstractText | Immunoglobulin heavy chain (IgH) locus-associated G-rich long noncoding RNA (SmuGLT) is important for physiological and pathological B cell DNA recombination. We demonstrate that the METTL3 enzyme-catalyzed N(6)-methyladenosine (m(6)A) RNA modification drives recognition and 3' end processing of SmuGLT 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(6)A reader YTHDC1. MPP6 and YTHDC1 promote CSR by recruiting AID and the RNA exosome to actively transcribe SmuGLT. Direct suppression of m(6)A modification of SmuGLT or of m(6)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(6)A modification, and m(6)A reader proteins in controlling long noncoding RNA processing, DNA recombination, and development in B cells. |
