Figure 1. The sequence of miRNAs controls their localization into exosomes.

(a) Microarray analysis of exosomal and cellular miRNAs from human primary T lymphocytes in resting and activated (PMA and ionomycin) conditions. The panel shows the heatmap of the per-row normalized expression levels of selected miRNAs differentially expressed in cells (CL) versus exosomes (EXOs) in resting (REST) or activated conditions (ACT). (b) Upper panel: Venn diagrams based on miRNA microarray results showing that activation-induced changes in miRNA profile are not the same in T cells and their derived exosomes. Lower panel: Venn diagrams based on miRNA microarray results showing that some miRNAs are always specifically sorted into exosomes (EXOmiRNAs, left panel) or specifically retained in cells (CLmiRNAs, right panel), independently of the activation state of the T cell. (c) Cladogram showing the multiple alignment of mature sequences of 30 EXOmiRNAs (red) and 42 CLmiRNAs (blue), revealing that miRNA clustering coincides with preferential localization in exosomes or cells. (d) Over-represented motifs in EXOmiRNAs (EXOmotifs, left panels) and CLmiRNAs (CLmotifs, right panels); ZOOPS model was used. For each data set, the remaining miRNAs annotated in Ensembl was used as background. A Markov model of order 0 was assumed for the background sequences. E-value <10⁻⁴.