Transient residence of the repulsive client Shutdown in Yb bodies plays a critical role in Piwi-piRISC biogenesis and maintaining fertility
Hirakata, S.; Fujita, A.; Siomi, M. C.
Show abstract
Nonmembranous organelles, such as Yb bodies in Drosophila ovarian somatic cells, form through liquid-liquid phase separation of scaffold proteins. Client proteins transiently accumulate in these organelles by binding to scaffolds. However, the regulation of this process is not well understood. Here, we investigate Shutdown, a client protein in Yb bodies, the site of Piwi-piRISC precursor (pre-Piwi-piRISC) formation. We found that Shutdown connects Armitage and Piwi in the cytosol to promote Piwi deposition to Yb bodies, before quickly returning to the cytosol. This return allows Armitage to transfer pre-Piwi-piRISC to the mitochondria for maturation. Shutdowns self-repulsion via its acidic N-terminus enables its transient residence in Yb bodies. A point mutation in Armitage, similar to a human Armitage/MOV10L1 mutation associated with azoospermia, traps Shutdown in Yb bodies, blocking Piwi-piRISC generation. This study reveals the mechanism of Shutdowns transient localization in Yb bodies and its essential role in Piwi-piRISC production and maintaining fertility.
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