A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay

Pengda Chen, Lianghua Lin, Xinyong Lin, Kunyu Liao, Jiali Qiang, Zhizhang Wang, Jianfeng Wu, Yang Li, Liang Yang, Nan Yao, Huilin Song, Yazhen Hong, Wen-Hsien Liu (), Yaoyang Zhang (), Xing Chang (), Dan Du () and Changchun Xiao ()
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Pengda Chen: Xiamen University
Lianghua Lin: Xiamen University
Xinyong Lin: Xiamen University
Kunyu Liao: Xiamen University
Jiali Qiang: Chinese Academy of Sciences
Zhizhang Wang: Westlake University
Jianfeng Wu: Xiamen University
Yang Li: Chinese Academy of Sciences
Liang Yang: Westlake University
Nan Yao: Westlake University
Huilin Song: Xiamen University
Yazhen Hong: Xiamen University
Wen-Hsien Liu: Xiamen University
Yaoyang Zhang: Chinese Academy of Sciences
Xing Chang: Westlake University
Dan Du: Xiamen University
Changchun Xiao: Xiamen University

Nature Communications, 2025, vol. 16, issue 1, 1-24

Abstract: Abstract Upon encountering antigens, B cells may undergo multiple differentiation paths, including becoming plasma cells and memory B cells. Although it is well-known that transcription factors govern gene expression programs underpinning these fate decisions in transcriptional level, the role of post-transcriptional regulators, with a focus on RNA-binding proteins, in the fate determination are lesser known. Here we find by RNA interactome capture-coupled CRISPR/Cas9 functional screening that the Csde1-Strap complex plays an important role in plasma cell differentiation. Mechanistically, the Csde1-Strap complex establishes the expression kinetics of Bach2, a key regulator of plasma cell differentiation. Bach2 expression is rapidly induced to promote B cell expansion and then decreased to initiate plasma cell differentiation. The Csde1-Strap interaction is critical for their binding to Bach2 mRNA to couple its decay with translation to restrain the magnitude and duration of Bach2 protein expression. In the absence of Csde1 or Strap, Bach2 translation is de-coupled from mRNA decay, leading to elevated and prolonged expression of Bach2 protein and impaired plasma cell differentiation. This study thus establishes the functional RBP landscape in B cells and illustrates the fundamental importance of controlling protein expression kinetics in cell fate determination.

Date: 2025
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DOI: 10.1038/s41467-025-58212-8

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