Alternative polyadenylation regulates CELF1/CUGBP1 target transcripts following T cell activation.

Area of Science:

• Molecular Biology
• Immunology
• Gene Regulation

Background:

• Alternative polyadenylation (APA) is a key mechanism controlling gene expression.
• APA-mediated transcript 3' end shortening occurs after T cell activation, but its functional impact remains unclear.
• GU-rich elements (GREs) in 3' UTRs recruit CELF1/CUGBP1 to promote mRNA decay.

Purpose of the Study:

• To investigate the role of APA in T cell activation.
• To elucidate the mechanism by which CELF1 influences APA site selection.
• To understand how APA affects the expression of CELF1 target genes involved in cell division.

Main Methods:

• Global RNA sequencing was employed to analyze APA site usage in T cells.
• CELF1 binding and its association with GREs were studied.
• The impact of APA on transcript expression levels was quantified.

Main Results:

• A network of CELF1 target genes crucial for cell division exhibited preferential 3' end shortening via APA post-T cell activation.
• This APA resulted in reduced CELF1 binding site inclusion and consequently, increased transcript expression.
• A model was proposed where CELF1 reversibly binds GREs to regulate APA site selection.

Conclusions:

• CELF1 plays a critical role in regulating APA site selection during T cell activation.
• APA-driven changes in transcript processing by CELF1 impact cellular proliferation.
• These findings offer insights into APA's role in development, oncogenesis, and immune responses.