Role of R-loop in antibody class switching and B cell lymphomagenesis

我们成功地将HNRNPU确定为IgH和cMyc基因座R-环的关键调节器。我们证实，在没有HNRNPU的情况下，由于C-NHEJ介导的修复缺陷，S-S重组受到损害。HNRNPU是CSR和B细胞染色体异常易位所必需的。主要的新发现概括如下：(1)机制研究表明，HNRNPU作为R环抑制因子，可能通过与来自IgH基因的生殖系转录本(GLT)结合而发挥作用。(2)另一条证据表明，这种与GLT的结合依赖于HNRNPU的C-末端，它明确地识别G-四链结构。(3)RNaseA处理也使HNRNPU与53BP1和Shilelton解离，表明HNRNPU通过RNA稳定C-NHEJ复合体。

We successfully identified HNRNPU as a critical modulator of the R-loop in the IgH and cMyc loci. We confirmed that S-S recombination was impaired in the absence of HNRNPU due to C-NHEJ-mediated repair defect. HNRNPU is required for both CSR and aberrant chromosomal translocation in B cells. Key new findings are summarized below_(1) Mechanistic study indicates that HNRNPU functions as an R-loop suppressing factor, possibly through binding to the germline transcript (GLT) derived from the IgH locus. (2) Another line of evidence suggests that this binding to GLT depends on HNRNPU’s C-terminal, which explicitly recognizes the G-quadruplex structure.(3) RNase A treatment also dissociates HNRNPU from 53BP1 and Shileldn, suggesting HNRNPU stabilizes the C-NHEJ complex through RNA.