3' Uridylation controls mature microRNA turnover during CD4 T-cell activation.
3' Uridylation controls mature microRNA turnover during CD4 T-cell activation.
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DOI：
10.1261/rna.060095.116
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发表时间：
2017-06
期刊：
影响因子：
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通讯作者：
Sánchez-Madrid F
中科院分区：
文献类型：
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作者：
Gutiérrez-Vázquez C;Enright AJ;Rodríguez-Galán A;Pérez-García A;Collier P;Jones MR;Benes V;Mizgerd JP;Mittelbrunn M;Ramiro AR;Sánchez-Madrid F
T淋巴细胞的活化需要microRNA（miRNA）表达的严格调节。末端尿苷酰转移酶（TUTases）催化3′非模板核苷酸加成（3′NTA）到miRNA上，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3′NTA成熟miRNA。在T细胞活化后，携带末端尿苷的miRNA序列特异性减少，伴随着TUT4和TUT7酶的下调。分析TUT4缺陷的T淋巴细胞，我们证明了这种末端尿苷酰转移酶对于维持稳定状态的T淋巴细胞的miRNA尿苷化是必不可少的。对合成的尿苷化miRNA的分析表明，在T细胞活化后，3′端添加尿苷促进了这些尿苷化miRNA的降解。我们的数据强调了转录后尿苷酸化作为T细胞活化过程中微调miRNA水平的机制。
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.