Fig. 1. The biogenesis and function of endogenous small RNAs in animals, and in plants and fungi. (A) In animals, microRNA (MIR) genes (top) are transcribed by Pol II into microRNA (miRNA) precursors, which are processed by DROSHA and DICER (DICER1) into miRNAs. The miRNAs are bound by an effector protein Argonaute (AGO) and cause the cleavage or translational inhibition of target mRNAs. In animals, despite the fact that each miRNA is able to regulate scores of target transcripts, genetic studies show that one major target underlies the role of a miRNA in a developmental process. Related miRNAs (light and dark blue) often have shared predicted targets, but genetic studies reveal that members of a miRNA family may have distinct developmental functions. (B) Endogenous siRNAs in S. pombe and in plants are generated from long transcripts from repeated DNA or transposons via the activities of RNA-dependent RNA polymerases (RdRP) and Dicer. Histone H3 lysine 9 (H3-K9) methylation and the siRNAs complexed with AGO act in a self-reinforcing loop to maintain heterochromatin at the loci. (C) Via an unknown mechanism, repeat-associated siRNAs (rasiRNAs) in Drosophila are produced from a master locus composed of multiple transposons. These small RNAs bind the Piwi subfamily of Argonaute proteins - Piwi, Aubergine (Aub) and AGO3 - and target homologous transposons scattered around the genome for silencing. An existing rasiRNA guides the cleavage of a target RNA through the slicer activity of the associated Piwi subfamily of Argonaute protein to lead to the production of a second rasiRNA.