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Siwi Cooperates with Par-1 Kinase to Resolve the Autoinhibitory Effect of Papi for Siwi-piRISC Biogenesis

Overview
Journal Nat Commun
Specialty Biology
Date 2022 Mar 22
PMID 35314687
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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 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.

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