Gutiérrez-Vázquez Cristina, Enright Anton J, Rodríguez-Galán Ana, Pérez-García Arantxa, Collier Paul, Jones Matthew R, Benes Vladimir, Mizgerd Joseph P, Mittelbrunn María, Ramiro Almudena R, Sánchez-Madrid Francisco
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.
RNA. 2017 Jun;23(6):882-891. doi: 10.1261/rna.060095.116. Epub 2017 Mar 28.
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.
T淋巴细胞的激活需要对微小RNA(miRNA)表达进行严格调控。末端尿苷转移酶(TUTases)催化miRNA的3'非模板化核苷酸添加(3'NTA),这可能影响miRNA的稳定性和功能。在此,我们通过深度测序研究了CD4 T淋巴细胞中成熟miRNA的3'NTA情况。在T细胞激活后,带有末端尿苷的miRNA序列特异性减少,同时TUT4和TUT7酶的表达下调。通过分析TUT4缺陷型T淋巴细胞,我们证明这种末端尿苷转移酶对于T淋巴细胞稳态下miRNA尿苷化的维持至关重要。对合成的尿苷化miRNA的分析表明,尿苷的3'添加促进了T细胞激活后这些尿苷化miRNA的降解。我们的数据强调转录后尿苷化是T细胞激活过程中微调miRNA水平的一种机制。