A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay
Pengda Chen1, Lianghua Lin1, Xinyong Lin1
1State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China.
Nature Communications
|March 26, 2025
Summary
The Csde1-Strap complex controls Bach2 protein levels, crucial for B cell differentiation into plasma cells. This RNA-binding protein complex ensures proper timing of Bach2 expression for effective B cell fate decisions.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- B cell differentiation into plasma cells is vital for antibody production.
- Transcription factors are known regulators of B cell fate, but post-transcriptional regulation is less understood.
- RNA-binding proteins (RBPs) play critical roles in post-transcriptional gene regulation.
Purpose of the Study:
- To investigate the role of RNA-binding proteins in B cell fate determination.
- To identify specific RBPs involved in plasma cell differentiation.
- To elucidate the molecular mechanisms by which RBPs control B cell differentiation.
Main Methods:
- RNA interactome capture coupled with CRISPR/Cas9 functional screening.
- Analysis of Csde1-Strap complex function in B cells.
- Investigation of Bach2 mRNA and protein expression kinetics.
Main Results:
- The Csde1-Strap complex is identified as a key regulator of plasma cell differentiation.
- This complex controls the expression kinetics of Bach2, a critical regulator.
- Csde1-Strap couples Bach2 mRNA decay with translation, restraining Bach2 protein levels.
- Loss of Csde1 or Strap leads to aberrant Bach2 expression and impaired plasma cell differentiation.
Conclusions:
- The Csde1-Strap complex is essential for precise control of protein expression kinetics during B cell differentiation.
- This study highlights the importance of post-transcriptional regulation by RBPs in cell fate determination.
- The findings establish a functional RBP landscape in B cells relevant to plasma cell differentiation.
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