Siwi Cooperates with Par-1 Kinase to Resolve the Autoinhibitory Effect of Papi for Siwi-piRISC Biogenesis
Overview
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Bombyx Papi acts as a scaffold for Siwi-piRISC biogenesis on the mitochondrial surface. Papi binds first to Siwi via the Tudor domain and subsequently to piRNA precursors loaded onto Siwi via the K-homology (KH) domains. This second action depends on phosphorylation of Papi. However, the underlying mechanism remains unknown. Here, we show that Siwi targets Par-1 kinase to Papi to phosphorylate Ser547 in the auxiliary domain. This modification enhances the ability of Papi to bind Siwi-bound piRNA precursors via the KH domains. The Papi S547A mutant bound to Siwi, but evaded phosphorylation by Par-1, abrogating Siwi-piRISC biogenesis. A Papi mutant that lacked the Tudor and auxiliary domains escaped coordinated regulation by Siwi and Par-1 and bound RNAs autonomously. Another Papi mutant that lacked the auxiliary domain bound Siwi but did not bind piRNA precursors. A sophisticated mechanism by which Siwi cooperates with Par-1 kinase to promote Siwi-piRISC biogenesis was uncovered.
Yamazaki H, Namba Y, Kuriyama S, Nishida K, Kajiya A, Siomi M Nat Commun. 2023; 14(1):1942.
PMID: 37029111 PMC: 10081994. DOI: 10.1038/s41467-023-37634-2.