title: 3' Uridylation controls mature microRNA turnover during CD4 T-cell activation.
abstract: Activation of T lymphocytes requires a tight regulation of microRNA (miRNA) expression. Terminal uridyltransferases (TUTases) catalyze 3' nontemplated nucleotide addition (3'NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T-cell activation, miRNA sequences bearing terminal uridines are specifically decreased, concomitantly with down-regulation of TUT4 and TUT7 enzymes. Analyzing TUT4-deficient T lymphocytes, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in the steady state of T lymphocytes. Analysis of synthetic uridylated miRNAs shows that 3' addition of uridine promotes degradation of these uridylated miRNAs after T-cell activation. Our data underline post-transcriptional uridylation as a mechanism to fine-tune miRNA levels during T-cell activation.
authors.affiliation: Instituto de Investigación Sanitaria Princesa, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.|Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid 28029, Spain.
authors.forename: Cristina
authors.identifier: 0000-0002-3846-4631
authors.initials: C
authors.lastname: Gutiérrez-Vázquez
authors.affiliation: European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom.
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Enright
authors.affiliation: Instituto de Investigación Sanitaria Princesa, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.|Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid 28029, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez-Galán
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid 28029, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Pérez-García
authors.affiliation: European Molecular Biology Laboratory (EMBL), Core Facilities and Services, Heidelberg 69117, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Collier
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: European Molecular Biology Laboratory (EMBL), Core Facilities and Services, Heidelberg 69117, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mizgerd
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid 28029, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Mittelbrunn
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid 28029, Spain.
authors.forename: Almudena R
authors.initials: AR
authors.lastname: Ramiro
authors.affiliation: Instituto de Investigación Sanitaria Princesa, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.|Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid 28029, Spain.|CIBER: Centro Investigación en Red Cardiovascular, Madrid 28029, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D020871:RNA Stability; D014529:Uridine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; D014529:Uridine
keywords: 3′ nontemplated nucleotides addition (3′NTA); CD4 T lymphocytes; Zcchc11 (TUT4); Zcchc6 (TUT7); isomiRs; microRNAs; uridylation