Activation of T lymphocytes requires a tight regulation of microRNAs (miRNAs) expression. Terminal uridyltransferases (TUTases) catalyze 3' non-templated nucleotide addition (3'NTA) to miRNAs which may influence miRNA stability and function. We investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T cell activation, uracil addition is specifically decreased, concomitantly with downregulation of TUT4 enzyme. By analyzing TUT4 deficient mice, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in steady state of T lymphocytes and established the requirement of TUT4 for a proper germinal center reaction. Analysis of synthetic uridylated miRNAs indicates that 3' addition of uridine promotes degradation of miRNAs after T cell activation. Our data support post-transcriptional uridylation as a mechanism to fine tune miRNA levels during T cell activation.. 3'uridylation controls mature miRNA turnover during T cell acti

Activation of T lymphocytes requires a tight regulation of microRNAs (miRNAs) expression. Terminal uridyltransferases (TUTases) catalyze 3' non-templated nucleotide addition (3'NTA) to miRNAs which may influence miRNA stability and function. We investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T cell activation, uracil addition is specifically decreased, concomitantly with downregulation of TUT4 enzyme. By analyzing TUT4 deficient mice, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in steady state of T lymphocytes and established the requirement of TUT4 for a proper germinal center reaction. Analysis of synthetic uridylated miRNAs indicates that 3' addition of uridine promotes degradation of miRNAs after T cell activation. Our data support post-transcriptional uridylation as a mechanism to fine tune miRNA levels during T cell activation.