Unfolding the Role of Splicing Factors and RNA Debranching in AID Mediated Antibody Diversification.

Unfolding the Role of Splicing Factors and RNA Debranching in AID Mediated Antibody Diversification. Int Rev Immunol. 2020 Sep 14;:1-18 Authors: Jaiswal A, Singh AK, Tamrakar A, Kodgire P Abstract Activated B-cells diversify their antibody repertoire via somatic hypermutation (SHM) and class switch recombination (CSR). SHM is restricted to the variable region, whereas, CSR is confined to the constant region of immunoglobulin (Ig) genes. Activation-induced cytidine deaminase (AID) is a crucial player in the diversification of antibodies in the activated B-cell. AID catalyzes the deamination of cytidine (C) into uracil (U) at Ig genes. Subsequently, low fidelity repair of U:G mismatches may lead to mutations. Transcription is essential for the AID action, as it provides a transient single-strand DNA substrate. Since splicing is a co-transcriptional event, various splicing factors or regulators influence the transcription. Numerous splicing factors are known to regulate the AID targeting, function, Ig transcription, and AID splicing, which eventually influence antibody diversification processes. Splicing regulator SRSF1-3, a splicing isoform of serine arginine-rich splicing factor (SRSF1), and CTNNBL1, a spliceosome interacting factor, interact with AID and play a critical role in SHM. Likewise, a splicing regulator polypyrimidine tract binding protein-2 (PTBP2) and the debranching enzyme (DBR1) debranches primary switch transcripts whi...
Source: International Reviews of Immunology - Category: Allergy & Immunology Tags: Int Rev Immunol Source Type: research