PDF(Pubmed)
Abstract：
The ATP-dependent RNA helicase UPF1 plays a crucial role in various mRNA degradation pathways, most importantly in nonsense-mediated mRNA decay (NMD). Here, we show that UPF1 is upregulated during the early stages of B cell development and is important for early B cell development in the bone marrow. B-cell-specific Upf1 deletion in mice severely impedes the early to late LPre-B cell transition, in which VH-DHJH recombination occurs at the Igh gene. Furthermore, UPF1 is indispensable for VH-DHJH recombination, without affecting DH-JH recombination. Intriguingly, the genetic pre-arrangement of the Igh gene rescues the differentiation defect in early LPre-B cells under Upf1 deficient conditions. However, differentiation is blocked again following Ig light chain recombination, leading to a failure in development into immature B cells. Notably, UPF1 interacts with and regulates the expression of genes involved in immune responses, cell cycle control, NMD, and the unfolded protein response in B cells. Collectively, our findings underscore the critical roles of UPF1 during the early LPre-B cell stage and beyond, thus orchestrating B cell development.
摘要：
ATP依赖性RNA解旋酶UPF1在各种mRNA降解途径中起着至关重要的作用。最重要的是无义介导的mRNA衰减（NMD）。这里,我们表明，UPF1在B细胞发育的早期阶段上调，对骨髓中的早期B细胞发育很重要。小鼠中B细胞特异性Upf1缺失严重阻碍了LPre-B细胞的早期到晚期转变，其中VH-DHJH重组发生在Igh基因。此外，UPF1是VH-DHJH重组不可缺少的，不影响DH-JH重组。有趣的是，在Upf1缺陷条件下，Igh基因的遗传预排列挽救了早期LPre-B细胞的分化缺陷。然而,分化在Ig轻链重组后再次被阻断，导致发育为未成熟B细胞的失败。值得注意的是,UPF1与参与免疫反应的基因相互作用并调节其表达，细胞周期控制，NMD,和B细胞中展开的蛋白质反应。总的来说，我们的发现强调了UPF1在早期LPre-B细胞阶段及以后的关键作用，从而协调B细胞的发育。
