Bursty gene expression and mRNA decay pathways orchestrate B cell activation
1Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92039, USA.
Science Advances
|December 3, 2021
Summary
Helix-loop-helix proteins E2A and E2-2 drive B cell activation by increasing gene expression. This involves higher transcriptional bursting and longer mRNA half-lives in activated B cells for a specific lineage program.
Area of Science:
- Immunology
- Molecular Biology
- Gene Regulation
Background:
- Helix-loop-helix transcription factors E2A and E2-2 are crucial for B cell activation.
- Understanding the regulation of E2A and E2-2 gene expression during B cell activation is essential.
Purpose of the Study:
- To investigate the regulatory mechanisms of E2A and E2-2 gene expression during B cell activation.
- To correlate changes in E2A and E2-2 mRNA levels with B cell activation and growth.
Main Methods:
- Analysis of E2A and E2-2 mRNA abundance in activated B cells.
- Assessment of transcriptional bursting frequencies and mRNA half-lives.
- Investigation of gene expression patterns in naïve versus activated B cells.
Main Results:
- E2A and E2-2 mRNA abundance increased concurrently with B cell activation and cell growth.
- Elevated mRNA levels were attributed to increased transcriptional bursting and prolonged mRNA half-lives.
- Increased bursting frequencies were observed at shared interchromosomal transcriptional hubs.
Conclusions:
- In naïve B cells, low bursting and high decay rates create noisy gene expression for rapid pathogen response.
- In activated B cells, increased bursting and reduced decay rates drive the B cell lineage gene program.
- Transcriptional bursting and mRNA stability are key regulators of E2A and E2-2 expression during B cell differentiation.
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