中文版 | English
Title

The RNA-binding protein hnRNP F is required for the germinal center B cell response

Author
Corresponding AuthorXu, Shengli; Ou, Xijun
Publication Years
2023-03-30
DOI
Source Title
EISSN
2041-1723
Volume14Issue:1
Abstract

["The germinal centre (GC) response is characterized by regulated production of high affinity, class-switched antibodies in response to T-cell dependent antigens. Here authors show that the GC response is not only regulated at the transcriptional and protein levels, but also by the RNA-binding protein hnRNP F via alternative splicing of the co-stimulatory molecule CD40.","The T cell-dependent (TD) antibody response involves the generation of high affinity, immunoglobulin heavy chain class-switched antibodies that are generated through germinal center (GC) response. This process is controlled by coordinated transcriptional and post-transcriptional gene regulatory mechanisms. RNA-binding proteins (RBPs) have emerged as critical players in post-transcriptional gene regulation. Here we demonstrate that B cell-specific deletion of RBP hnRNP F leads to diminished production of class-switched antibodies with high affinities in response to a TD antigen challenge. B cells deficient in hnRNP F are characterized by defective proliferation and c-Myc upregulation upon antigenic stimulation. Mechanistically, hnRNP F directly binds to the G-tracts of Cd40 pre-mRNA to promote the inclusion of Cd40 exon 6 that encodes its transmembrane domain, thus enabling appropriate CD40 cell surface expression. Furthermore, we find that hnRNP A1 and A2B1 can bind to the same region of Cd40 pre-mRNA but suppress exon 6 inclusion, suggesting that these hnRNPs and hnRNP F might antagonize each-other's effects on Cd40 splicing. In summary, our study uncovers an important posttranscriptional mechanism regulating the GC response."]

URL[Source Record]
Indexed By
Language
English
Important Publications
NI Journal Papers
SUSTech Authorship
First ; Corresponding
Funding Project
Shenzhen Science and Technology Innovation Commission[
WOS Research Area
Science & Technology - Other Topics
WOS Subject
Multidisciplinary Sciences
WOS Accession No
WOS:000961133600029
Publisher
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:0
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/527711
DepartmentSchool of Life Sciences
工学院
工学院_计算机科学与工程系
Affiliation
1.Southern Univ Sci & Technol, Sch Life Sci, Shenzhen 518055, Peoples R China
2.Taizhou Univ, Med Sch, Taizhou 318000, Peoples R China
3.Southern Univ Sci & Technol, Coll Engn, Dept Comp Sci & Engn, Shenzhen 518055, Peoples R China
4.Agcy Sci Technol & Res, Singapore Immunol Network, Singapore 138648, Singapore
5.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117599, Singapore
First Author AffilicationSchool of Life Sciences
Corresponding Author AffilicationSchool of Life Sciences
First Author's First AffilicationSchool of Life Sciences
Recommended Citation
GB/T 7714
Huang, Hengjun,Li, Yuxing,Zhang, Gaopu,et al. The RNA-binding protein hnRNP F is required for the germinal center B cell response[J]. NATURE COMMUNICATIONS,2023,14(1).
APA
Huang, Hengjun.,Li, Yuxing.,Zhang, Gaopu.,Ruan, Gui-Xin.,Zhu, Zhijian.,...&Ou, Xijun.(2023).The RNA-binding protein hnRNP F is required for the germinal center B cell response.NATURE COMMUNICATIONS,14(1).
MLA
Huang, Hengjun,et al."The RNA-binding protein hnRNP F is required for the germinal center B cell response".NATURE COMMUNICATIONS 14.1(2023).
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