Mechanism of noncoding RNA-associated N⁶-methyladenosine recognition by an RNA processing complex during IgH DNA recombination.

ABSTRACT: 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 N⁶-methyladenosine (m⁶A) 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 m⁶A reader YTHDC1. MPP6 and YTHDC1 promote CSR by recruiting AID and the RNA exosome to actively transcribe SμGLT. Direct suppression of m⁶A modification of SμGLT or of m⁶A reader YTHDC1 reduces CSR. Moreover, METTL3, an essential gene for B cell development

SUBMITTER: Nair L 

PROVIDER: S-EPMC8571800 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature