eIF3a function in immunity and protection against severe sepsis by regulating B cell quantity and function through m6A modification

eIF3a function in immunity and protection against severe sepsis by regulating B cell quantity and function through m6A modification

eIF3a is a N6-methyladenosine (m6A) reader that regulates mRNA translation by recognizing m6A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m6A during infection when canonical cap-dependent initiation is inhibited....

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Main Authors: Qianying Ouyang, Jiajia Cui, Yang Wang, Ke Liu, Yan Zhan, Wei Zhuo, Juan Chen, Honghao Zhou, Chenhui Luo, Jianming Xia, Liansheng Wang, Chengxian Guo, Jianting Zhang, Zhaoqian Liu, Jiye Yin
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Acta Pharmaceutica Sinica B
Subjects:
eIF3a
m6A
Sepsis
B cell
RNA modification
Infection
Online Access:http://www.sciencedirect.com/science/article/pii/S2211383525000383
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Summary:eIF3a is a N6-methyladenosine (m6A) reader that regulates mRNA translation by recognizing m6A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m6A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m6A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.
ISSN:2211-3835

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