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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
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PABPC1 Modulates Immunoglobulin pre-mRNA Alternative Polyadenylation.

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    Poly(A)-binding protein C1 (PABPC1) regulates gene expression by shortening 3' untranslated regions and downregulating target genes, particularly impacting B cell development and immunoglobulin secretion.

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    Area of Science:

    • Molecular Biology
    • Gene Regulation
    • Immunology

    Background:

    • Alternative polyadenylation (APA) is crucial for tuning gene expression and its dysregulation is linked to disease.
    • The precise role of Poly(A)-binding protein C1 (PABPC1) in gene regulation and APA is not well-defined.
    • APA significantly influences immunoglobulin secretion during B cell development.

    Purpose of the Study:

    • To elucidate the function of PABPC1 in B cell development.
    • To map PABPC1-RNA interactions and its impact on APA.
    • To understand PABPC1's role in regulating gene expression.

    Main Methods:

    • Crosslinking, Ligation, and Sequencing (CLAP-seq) to map PABPC1-RNA interactions.
    • Degron-based strategy to perturb PABPC1 expression.
    • Integration with transcriptomic data and genomics modeling.

    Main Results:

    • PABPC1 binds to A-rich regions in the 3' UTR of 70% of its gene targets.
    • PABPC1 downregulates approximately 60% of its target genes.
    • PABPC1 binding is enriched in genes with shortened 3' UTRs and is associated with decreased gene expression, particularly near the polyadenylation site (PAS).

    Conclusions:

    • PABPC1 primarily functions to shorten 3' UTRs and downregulate gene expression in a context-dependent manner.
    • PABPC1's role in immunoglobulin transcript APA and secretion is modest but specific.
    • Findings clarify PABPC1's contribution to gene regulation via APA.