Schematic representation of the microRNA biogenesis machinery. Schematic representation of the microRNA biogenesis machinery. A: nuclear biogenesis of pre-microRNA (miRNA) forms miRNA encoding genes through the transcription of pri-miRNA or directly forms intronic miRNA. This mechanism is PolIII dependent and requires the presence of Drosha/DGCR8. B: pre-miRNAs are exported to the cytoplasm through an Exportin 5-dependent mechanism and there, the pre-miRNA is processed by Dicer into a miRNA duplex and loaded to the RNA-induced silencing complex (RISC) complex. C: alternatively, it has been recently shown that pre-miRNAs were degraded by IRE1 endoribonuclease. AGO, argonaute protein. Marion Maurel, and Eric Chevet Am J Physiol Cell Physiol 2013;304:C1117-C1126 ©2013 by American Physiological Society