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Title: Muskelin is a substrate adaptor of the highly regulated Drosophila embryonic CTLH E3 ligase
Abstract The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that inDrosophilathe deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies becauseDrosophilalacks an identifiable substrate adaptor, and the mechanisms restricting the degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental regulation of the CTLH complex is multi-pronged, including transcriptional control by OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate is a substrate adaptor for theDrosophilaCTLH complex. Finally, we find that Muskelin has few targets beyond the three known RNA-binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, during which time it regulates three important RNA-binding proteins.  more » « less
Award ID(s):
2046136
PAR ID:
10572753
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Publisher / Repository:
Nature Publishing Group
Date Published:
Journal Name:
EMBO Reports
Volume:
26
Issue:
6
ISSN:
1469-3178
Format(s):
Medium: X Size: p. 1647-1669
Size(s):
p. 1647-1669
Sponsoring Org:
National Science Foundation
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