Siwi cooperates with Par-1 kinase to resolve the autoinhibitory effect of Papi for Siwi-piRISC biogenesis.

ABSTRACT: 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 tha

SUBMITTER: Yamada H 

PROVIDER: S-EPMC8938449 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature