Biology of Non-coding RNA

Figure 1. RNAi Pathways
Substrate RNA molecules that give rise to small RNA (sRNA) species are depicted in blue, sRNAs are depicted in black, and target RNA transcripts are depicted in red. (A) A ‘‘canonical’’ RNAi pathway. Examples of this pathway are the endo-siRNA pathways in Drosophila and mammals. In both systems, Ago2 is most likely the AGO protein involved.
(B) dsRNA can be generated by an RNA-directed RNA polymerase (RdRP). This mechanism occurs in S. pombe and in C. elegans. (C) RdRP enzymes can also directly generate short RNA molecules that are bound by AGO proteins. This mode of small RNA generation occurs in C. elegans. The AGO proteins accepting this type of small RNA do not appear to direct target RNA cleavage but do result in a drop in RNA target levels. (D) A model of piRNA biogenesis and function. Single-stranded RNA serves as a source of small RNA and cleavage by either Piwi proteins or an unknown nuclease generates the 50 ends of the small RNAs. Primary piRNAs carry a 50-uracil residue, whereas secondary piRNAs either have a 50-uracil or an adenosine at position 10, due to the cleavage characteristics of AGO proteins. The processing of the 3’ end is poorly understood but is finalized by methylation of the 20OH group of the last nucleotide. Piwi proteins can cleave their targets, but whether this is required for their silencing activity is not well known. Note that it is difficult to separate target RNA molecules from piRNA substrates, due to the cyclical nature of the process. (E) Potential models of how piRNAs are generated in C. elegans (21U RNAs). A motif (represented as ‘‘xxx’’) is found upstream of 21U RNAs. This motif may function as an RNA processing signal or as a transcriptional signal. Processing of the 30 end likely resembles the other Piwi pathways. Not much is known about how 21U RNAs silence their targets, but at least in some cases, an RdRP appears to be recruited, triggering the pathway depicted in (C).
From: Ketting, Developmental Cell, 2011