title: CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204.
abstract: T lymphocytes stimulated through their antigen receptor (TCR) preferentially express mRNA isoforms with shorter 3´ untranslated regions (3´-UTRs) derived from alternative pre-mRNA cleavage and polyadenylation (APA). However, the physiological relevance of APA programs remains poorly understood. CD5 is a T-cell surface glycoprotein that negatively regulates TCR signaling from the onset of T-cell activation. CD5 plays a pivotal role in mediating outcomes of cell survival or apoptosis, and may prevent both autoimmunity and cancer. In human primary T lymphocytes and Jurkat cells we found three distinct mRNA isoforms encoding CD5, each derived from distinct poly(A) signals (PASs). Upon T-cell activation, there is an overall increase in CD5 mRNAs with a specific increase in the relative expression of the shorter isoforms. 3´-UTRs derived from these shorter isoforms confer higher reporter expression in activated T cells relative to the longer isoform. We further show that polypyrimidine tract binding protein (PTB/PTBP1) directly binds to the proximal PAS and PTB siRNA depletion causes a decrease in mRNA derived from this PAS, suggesting an effect on stability or poly(A) site selection to circumvent targeting of the longer CD5 mRNA isoform by miR-204. These mechanisms fine-tune CD5 expression levels and thus ultimately T-cell responses.
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
authors.forename: Rita G
authors.initials: RG
authors.lastname: Domingues
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Lago-Baldaia
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pereira-Castro
authors.affiliation: Department of Molecular Physiology and Biophysics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Fachini
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cell Activation and Gene Expression Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Oliveira
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Danica
authors.initials: D
authors.lastname: Drpic
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
authors.forename: Nair
authors.initials: N
authors.lastname: Lopes
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
authors.forename: Telmo
authors.initials: T
authors.lastname: Henriques
authors.affiliation: Department of Molecular Physiology and Biophysics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Neilson
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cell Activation and Gene Expression Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.|ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal.
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Carmo
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moreira
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D018956:CD5 Antigens / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology*; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D011061:Poly A; D026723:Polyadenylation; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D034622:RNA Interference; D059368:RNA Isoforms; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D018956:CD5 Antigens; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; C450006:PTBP1 protein, human; D059368:RNA Isoforms; D012333:RNA, Messenger; D038941:Polypyrimidine Tract-Binding Protein; D011061:Poly A
keywords: CD5 ⋅ Alternative polyadenylation ⋅ PTB/PTBP1 ⋅ miR-204 ⋅ T-lymphocyte activation