UPF1 plays critical roles in early B cell development.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38982067.
- Also identified by DOI 10.1038/s41467-024-50032-6 and PMC identifier 11233602.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 V<sub>H</sub>-D<sub>H</sub>J<sub>H</sub> recombination occurs at the Igh gene. Furthermore, UPF1 is indispensable for V<sub>H</sub>-D<sub>H</sub>J<sub>H</sub> recombination, without affecting D<sub>H</sub>-J<sub>H</sub> 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.
Medical subject headings
- B-Lymphocytes
- Cell Differentiation
- Nonsense Mediated mRNA Decay
- RNA Helicases