TY - JOUR
T1 - Siwi cooperates with Par-1 kinase to resolve the autoinhibitory effect of Papi for Siwi-piRISC biogenesis
AU - Yamada, Hiromi
AU - Nishida, Kazumichi M.
AU - Iwasaki, Yuka W.
AU - Isota, Yosuke
AU - Negishi, Lumi
AU - Siomi, Mikiko C.
N1 - Funding Information:
We thank H. Siomi, S. Yamanaka, H. Yamazaki, S. Hirakata, Y. Namba, and R. Onishi for reading the manuscript and providing useful comments. We also thank all other members of the Siomi laboratory at The University of Tokyo. This study was supported by research grants from MEXT to M.C.S. (19H05466), K.M.N. (20K06483), and Y.W.I. (21H00259). H.Y. is supported by the Japan Society for the Promotion of Science (19J13939), and Y.W.I. is supported by JST PRESTO (JPMJPR20E2).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-022-29193-9
DO - 10.1038/s41467-022-29193-9
M3 - Article
C2 - 35314687
AN - SCOPUS:85126824976
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1518
ER -