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3′ Uridylation controls mature microRNA turnover during CD4 T-cell activation

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 lymphoc...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435861/
https://www.ncbi.nlm.nih.gov/pubmed/28351886
http://dx.doi.org/10.1261/rna.060095.116
Descripción
Sumario: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.