Regulation of CUG-binding protein 1 (CUGBP1) binding to target transcripts upon T cell activation

Daniel Beisang1, Bernd Rattenbacher, Irina A Vlasova-St Louis

  • 1Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Insights

CUG-binding protein 1 (CUGBP1) regulates gene expression in T cells. Upon activation, CUGBP1 phosphorylation reduces its RNA binding, altering target gene expression critical for cell activation and proliferation.

Area of Science:

  • Molecular Biology
  • Immunology
  • Gene Regulation

Background:

  • CUG-binding protein 1 (CUGBP1) is an RNA-binding protein controlling gene expression via splicing, degradation, and translation.
  • Understanding CUGBP1's role in T cell activation is crucial for deciphering immune responses.

Purpose of the Study:

  • To identify cytoplasmic mRNA targets of CUGBP1 in human T cells.
  • To investigate how T cell activation affects CUGBP1 binding to its targets.

Main Methods:

  • RNA immunoprecipitation followed by microarray analysis (RIP-chip).
  • Analysis of CUGBP1 target enrichment for GU-rich elements (GREs) in 3'-UTRs.
  • Assessment of CUGBP1 phosphorylation and RNA binding during T cell activation.

Main Results:

  • CUGBP1 targets are enriched for GREs in their 3'-UTRs.
  • T cell activation leads to decreased CUGBP1 binding to target RNAs due to phosphorylation.
  • Many CUGBP1 targets show transient up-regulation upon activation, encoding proteins for cellular activation and proliferation.

Conclusions:

  • CUGBP1 plays a significant role in regulating gene expression during T cell activation.
  • Activation-dependent phosphorylation of CUGBP1 modulates its RNA-binding activity.
  • CUGBP1 influences the expression of key regulatory proteins required for T cell activation and proliferation.

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