{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T03:36:18Z","timestamp":1774064178062,"version":"3.50.1"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"FEDER - Fundo Europeu de Desenvolvimento Regional funds"},{"name":"FCT"},{"name":"American-Portuguese Biomedical Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>T lymphocytes stimulated through their antigen receptor (TCR) preferentially express mRNA isoforms with shorter 3\u00b4 untranslated regions (3\u00b4\u2010UTRs) derived from alternative pre\u2010mRNA cleavage and polyadenylation (APA). However, the physiological relevance of APA programs remains poorly understood. CD5 is a T\u2010cell surface glycoprotein that negatively regulates TCR signaling from the onset of T\u2010cell 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\u2010cell activation, there is an overall increase in <jats:italic>CD5<\/jats:italic> mRNAs with a specific increase in the relative expression of the shorter isoforms. 3\u00b4\u2010UTRs 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 <jats:italic>CD5<\/jats:italic> mRNA isoform by miR\u2010204. These mechanisms fine\u2010tune CD5 expression levels and thus ultimately T\u2010cell responses.<\/jats:p>","DOI":"10.1002\/eji.201545663","type":"journal-article","created":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T07:08:37Z","timestamp":1458716917000},"page":"1490-1503","source":"Crossref","is-referenced-by-count":41,"title":["CD5 expression is regulated during human T\u2010cell activation by alternative polyadenylation, PTBP1, and miR\u2010204"],"prefix":"10.1002","volume":"46","author":[{"given":"Rita G.","family":"Domingues","sequence":"first","affiliation":[{"name":"Gene Regulation Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"}]},{"given":"In\u00eas","family":"Lago\u2010Baldaia","sequence":"additional","affiliation":[{"name":"Gene Regulation Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"}]},{"given":"Isabel","family":"Pereira\u2010Castro","sequence":"additional","affiliation":[{"name":"Gene Regulation Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto  Portugal"}]},{"given":"Joseph M.","family":"Fachini","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Dan L. Duncan Cancer Center Baylor College of Medicine  Houston TX USA"}]},{"given":"Liliana","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto  Portugal"},{"name":"Cell Activation and Gene Expression Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"}]},{"given":"Danica","family":"Drpic","sequence":"additional","affiliation":[{"name":"Gene Regulation Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto  Portugal"}]},{"given":"Nair","family":"Lopes","sequence":"additional","affiliation":[{"name":"Gene Regulation Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"}]},{"given":"Telmo","family":"Henriques","sequence":"additional","affiliation":[{"name":"Gene Regulation Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"}]},{"given":"Joel R.","family":"Neilson","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Dan L. Duncan Cancer Center Baylor College of Medicine  Houston TX USA"}]},{"given":"Alexandre M.","family":"Carmo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto  Portugal"},{"name":"Cell Activation and Gene Expression Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto  Portugal"}]},{"given":"Alexandra","family":"Moreira","sequence":"additional","affiliation":[{"name":"Gene Regulation Group IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto  Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto  Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto  Portugal"}]}],"member":"311","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(94)90165-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4049\/jimmunol.136.2.505","article-title":"Leu\u20101+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen: phenotypic and functional studies","volume":"136","author":"Antin J. H.","year":"1986","journal-title":"J. Immunol."},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.4049\/jimmunol.133.2.724","article-title":"Biologic functions of the OKT1 T cell surface antigen. I. The T1 molecule is involved in helper function","volume":"133","author":"Thomas Y.","year":"1984","journal-title":"J. Immunol."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7542801"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.230102"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199805)28:05<1617::AID-IMMU1617>3.0.CO;2-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.4.2903"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2301"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.9.5464"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3043"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.011"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202408109"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100301.064833"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2008.11.007"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.5.2928"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0205059"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3662"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00617-7"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.1999.tb00400.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1128\/MMBR.63.2.405-445.1999","article-title":"Formation of mRNA 3\u2018 ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis","volume":"63","author":"Zhao J.","year":"1999","journal-title":"Microbiol. Mol. Biol. Rev"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.116"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2288"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.11.029"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900028106"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07488"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.016"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.146886.112"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155390"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.08.017"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601932"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3482"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.47"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20120044"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.10.4174-4183.2004"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.16.2522"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058879"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601699"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.577707"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp470"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6465"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.156919.113"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki055"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts199"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.10.7.1001"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.01.011"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq444"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.1.78"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201489852"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2005.07.018"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00050.x"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.156"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.8.4478"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003236"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm931"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.21.9595-9607.2005"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.039"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-125856"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1030"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.08.016"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-105"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.019"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0b013e318247bc64"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.22841"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201545663","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201545663","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T22:31:30Z","timestamp":1696631490000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201545663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,15]]},"references-count":64,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1002\/eji.201545663"],"URL":"https:\/\/doi.org\/10.1002\/eji.201545663","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,15]]}}}