CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Alternative pre-mRNA cleavage and polyadenylation (APA) generates mRNA isoforms with varying 3´-UTRs.
• CD5 is a T-cell surface glycoprotein crucial for regulating T-cell receptor (TCR) signaling and immune responses.
• The physiological significance of APA in T-cell activation, particularly for CD5, is not well understood.

Purpose of the Study:

• To investigate the role of APA in regulating CD5 mRNA expression during T-cell activation.
• To identify the mechanisms controlling CD5 mRNA isoform selection.
• To understand how these mechanisms influence T-cell responses.

Main Methods:

• Analysis of CD5 mRNA isoforms in human primary T lymphocytes and Jurkat cells.
• Reporter assays to assess the functional impact of different 3´-UTRs.
• RNA-binding protein analysis, including siRNA depletion of polypyrimidine tract binding protein (PTB/PTBP1).

Main Results:

• Three distinct CD5 mRNA isoforms, generated from different poly(A) signals (PASs), were identified.
• T-cell activation led to an increase in overall CD5 mRNA, with a preferential rise in shorter isoforms.
• Shorter isoforms conferred higher reporter expression in activated T cells, and PTB/PTBP1 binding to a proximal PAS influenced isoform expression.

Conclusions:

• APA programs play a significant role in regulating CD5 expression during T-cell activation.
• The selection of specific CD5 mRNA isoforms, influenced by factors like PTB/PTBP1, fine-tunes T-cell signaling.
• These APA-mediated mechanisms contribute to the precise control of T-cell responses, potentially impacting autoimmunity and cancer.