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Updated: May 27, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
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.
Abstract:
The RNA-binding protein, CUG-binding protein 1 (CUGBP1), regulates gene expression at the levels of alternative splicing, mRNA degradation, and translation. We used RNA immunoprecipitation followed by microarray analysis to identify the cytoplasmic mRNA targets of CUGBP1 in resting and activated primary human T cells and found that CUGBP1 targets were highly enriched for the presence of GU-rich elements (GREs) in their 3'-untranslated regions. The number of CUGBP1 target transcripts decreased dramatically following T cell activation as a result of activation-dependent phosphorylation of CUGBP1 and decreased ability of CUGBP1 to bind to GRE-containing RNA. A large percentage of CUGBP1 target transcripts exhibited rapid and transient up-regulation, and a smaller percentage exhibited transient down-regulation following T cell activation. Many of the transiently up-regulated CUGBP1 target transcripts encode important regulatory proteins necessary for transition from a quiescent state to a state of cellular activation and proliferation. Overall, our results show that CUGBP1 binding to certain GRE-containing target transcripts decreased following T cell activation through activation-dependent phosphorylation of CUGBP1.
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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