UPF1 plays critical roles in early B cell development

Noriki Iwai, Kotaro Akaki, Fabian Hia, Wei Li, Masanori Yoshinaga, Takashi Mino () and Osamu Takeuchi ()
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Noriki Iwai: Kyoto University
Kotaro Akaki: Kyoto University
Fabian Hia: Kyoto University
Wei Li: Kyoto University
Masanori Yoshinaga: Kyoto University
Takashi Mino: Kyoto University
Osamu Takeuchi: Kyoto University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50032-6

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