Fig. 7. Model for sDMA regulation and its function in ping-pong cycle.

a Model sDMA dependent assembly of the ping processing complex. The N-terminus of unloaded Aub is inaccessible. Binding to piRNA guide leads to a conformational change of Aub exposing its N terminus and enabling methylation of its N-terminal arginines. Methylation thus serves as a signal of loading-state and enables Aub binding to the Tud2 domain of Krimper, which specifically recognizes methylated Arginines. The Tud1 domain of Krimper binds unmethylated, unloaded Ago3, enabling Ago3 loading with the newly processed piRNA. The N-terminal unstructured region of Krimper allows Krimper multimerization resulting in a Krimper scaffold that might assist in nuage assembly and ensuring high local concentration of Aub and Ago3. b The Ping-Pong cycle consists of two distinct stages. In the ping stage, Aub with its piRNA guide targets piRNA precursors or TE transcripts. Cleaved, mature piRNA is loaded into Ago3. In the pong stage, piRNA-loaded Ago3 targets antisense piRNA precursors. Cleaved mature piRNA is loaded into Aub. The ping and pong processing could be accomplished by different complexes in nuage.