T helper cells exhibit a dynamic and reversible 3'-UTR landscape.

Area of Science:

• Immunology
• Molecular Biology
• RNA Biology

Background:

• 3' untranslated regions (3' UTRs) regulate mRNA fate through RNA-binding protein (RBP) and microRNA interactions.
• T cells exhibit dynamic 3' UTR modifications upon activation, but their functional significance remains unclear.

Purpose of the Study:

• Investigate division-dependent alternative polyadenylation (APA) in T helper cells.
• Determine the impact of 3' UTR dynamics on gene expression and RNA regulation during T cell activation and expansion.

Main Methods:

• Generated 3' end sequencing data from various CD4+ T cell subsets (naive, activated, memory, regulatory).
• Estimated 3' UTR length changes using nonnegative matrix factorization and PacBio long-read sequencing.
• Analyzed bulk RNA-seq data to assess the association between APA and gene expression.

Main Results:

• APA events in T cells were found to be transient, reverting after effector phase expansion.
• No significant association was observed between APA and differential gene expression or transcript usage.
• Conserved binding sites for T cell-relevant microRNAs and RBPs were identified in alternative 3' UTRs.

Conclusions:

• Alternative polyadenylation in T cells plays a marginal role in regulating overall transcript abundance.
• 3' UTR sequence modifications, particularly RBP and microRNA binding sites, are crucial for controlling T cell fate and homeostasis.