The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes

Activation-induced (cytidine) deaminase
DOI: 10.1038/s41422-018-0076-9 Publication Date: 2018-08-24T06:26:48Z
ABSTRACT
Abstract Activation-induced cytidine deaminase (AID) mediates class switching by binding to a small fraction of single-stranded DNA (ssDNA) diversify the antibody repertoire. The precise mechanism for highly selective AID targeting in genome has remained elusive. Here, we report an RNA-binding protein, ROD1 (also known as PTBP3 ), that is both required and sufficient define AID-binding sites genome-wide activated B cells. interacts with via ultraconserved loop, which proves be critical recruitment ssDNA using bi-directionally transcribed nascent RNAs stepping stones. Strikingly, AID-specific mutations identified human patients hyper-IgM syndrome type 2 (HIGM2) completely disrupt interacting surface ROD1, thereby abolishing immunoglobulin ( Ig ) loci. Together, our results suggest RNA traps protein serves guiding system load onto specific genomic loci induce rearrangement during immune responses.
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