title: Alternative polyadenylation regulates CELF1/CUGBP1 target transcripts following T cell activation.
abstract: Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for regulating gene expression. Transcript 3' end shortening through changes in polyadenylation site usage occurs following T cell activation, but the consequences of APA on gene expression are poorly understood. We previously showed that GU-rich elements (GREs) found in the 3' untranslated regions of select transcripts mediate rapid mRNA decay by recruiting the protein CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of CELF1 target transcripts involved in cell division underwent preferential 3' end shortening via APA following T cell activation, resulting in decreased inclusion of CELF1 binding sites and increased transcript expression. We present a model whereby CELF1 regulates APA site selection following T cell activation through reversible binding to nearby GRE sequences. These findings provide insight into the role of APA in controlling cellular proliferation during biological processes such as development, oncogenesis and T cell activation.
authors.affiliation: Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA; Department of Microbiology, University of Minnesota, Minneapolis, MN, USA. Electronic address: beis0051@umn.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Beisang
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA. Electronic address: cavanr@biostat.umn.edu.
authors.forename: Cavan
authors.initials: C
authors.lastname: Reilly
authors.affiliation: Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA; Department of Microbiology, University of Minnesota, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA. Electronic address: Bohja001@umn.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Bohjanen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing; D001665:Binding Sites / Q000235:genetics; D000067879:CELF1 Protein; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008957:Models, Genetic; D011061:Poly A / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D020413:3' Untranslated Regions; D000067879:CELF1 Protein; C102843:CELF1 protein, human; D016601:RNA-Binding Proteins; D011061:Poly A
keywords: Alternative polyadenylation; CELF1; CUGBP1; Cell division; GRE; T cell stimulation; mRNA decay