Biosynthesis and proposed secretion pathways of miRNAs in human cells. The miRNA precursors are synthesized in the nucleus a processed by specific nucleases to engage the RISC complex and exert their negative regulatory activity over mRNA transcripts. MiRNA secretion routes are still not totally clear, but at least two RNA-binding proteins, YBX1 and mSMase2, have been described to be involved in the specific recruitment of miRNAs into multi-vesicular bodies and further into exosomes. However, miRNAs can be also found in biofluids in the form of free Ago2-complexes, within microparticles, and complexed with plasma proteins, and in these cases the secretion routes are not known. The secretion pathways for other ncRNAs such as lncRNAs and circRNAs remain uncharacterized.