Regulation of CUG-binding Protein 1 (CUGBP1) Binding to Target Transcripts upon T Cell Activation

Abstract

Background:We identified target transcripts of the RNA-binding protein CUGBP1 in resting and activated T cells. Results: T cell activation induced CUGBP1 phosphorylation, causing decreased CUGBP1 binding to target transcripts. Conclusion: CUGBP1 binding to a network of target transcripts is regulated by CUGBP1 phosphorylation following T cell activation. Significance: CUGBP1 target transcripts are coordinately regulated during T cell activation.

CELF1, a Multifunctional Regulator of Posttranscriptional Networks

“…During the process of T cell activation, phosphorylation of CELF1 alters binding by CELF1 to target transcripts. Shortly following T cell activation, CELF1 becomes phosphorylated, dramatically decreasing its affinity for mRNA and leading to stabilization of CELF1 target transcripts [77]. Overall, these studies show that phosphorylation regulates the many functions of CELF1 in posttranscriptional gene regulation.…”

“…In primary human T cells, GREs and CELF1 appear to be involved in the rapid changes in gene expression patterns observed following T cell receptor-mediated activation. Identification the cytoplasmic binding targets of CELF1 before and after T cell activation led to the discovery that CELF1 dissociated from GREcontaining transcripts following T cell activation in a manner correlated with a transient upregulation of CELF1 target mRNAs [77]. The dissociation of CELF1 from its target transcripts upon T cell activation was the result of an activation-dependent phosphorylation of CELF1 and a resultant decrease in the ability of CELF1 to bind to GRE-containing RNAs [77].…”

“…In this work, the authors proposed a 15-nucleotide consensus motif (UGU/UG)3 to be the target motif of EDEN-BP [85], [86]. The RIP-Chip approach was also used to investigate the cytoplasmic target transcripts of CELF1 in resting and activated primary human T cells, and target transcripts were highly enriched for the presence of the GRE in their 3'UTRs, but the number of CELF1 target transcripts decreased dramatically following T cell activation [77]. Overall, numerous CELF1 target transcripts have been identified in several different systems indicating the CELF1 functions to regulate an important posttranscriptional network of gene expression.…”

“…Using this methodology, CELF1 targets have been identified in HeLa cells, resting and activated human T cells, and mouse myoblasts [55], [77], [82].…”

“…CELF1 is a known phosphoprotein with multiple predicted phosphorylation sites, and CELF1 phosphorylation appears to regulate its function as a mediator of alternative splicing, mRNA decay, and translational regulation [74], [75], [76], [77]. One of the pathologic events which occurs in the disease Myotonic Dystrophy type 1 (DM1) is an increase in the protein abundance of CELF1 and an associated increase in CELF1 mediated alternative splicing activity.…”