Precise Temporal Regulation of Post-transcriptional Repressors Is Required for an Orderly Drosophila Maternal-to-Zygotic Transition

In animal embryos, the maternal-to-zygotic transition (MZT) hands developmental control from maternal to zygotic gene products. We show that the maternal proteome represents more than half of the protein-coding capacity of Drosophila melanogaster’s genome, and that 2% of this proteome is rapidly degraded during the MZT. Cleared proteins include the post-transcriptional repressors Cup, Trailer hitch (TRAL), Maternal expression at 31B (ME31B), and Smaug (SMG). Although the ubiquitin-proteasome system is necessary for clearance of these repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL, and ME31B for degradation early in the MZT and the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. Deleting the C-terminal 233 amino acids of SMG abrogates F-box protein interaction and confers immunity to degradation. Persistent SMG downregulates zygotic re-expression of mRNAs whose maternal contribution is degraded by SMG. Thus, clearance of SMG permits an orderly MZT. [Display omitted] •Early Drosophila embryos degrade 2% of their maternally encoded proteome•The Cup-TRAL-ME31B-Smaug post-transcriptional repressive complex is cleared•Distinct E3 ubiquitin ligases target Cup-TRAL-ME31B (CTLH E3) versus Smaug (SCF E3)•Failure to degrade Smaug abrogates an orderly maternal-to-zygotic transition Cao et al. show that 2% of the proteome is degraded in early Drosophila embryos, including a repressive ribonucleoprotein complex. Two E3 ubiquitin ligases separately act on distinct components of this complex to phase their clearance. Failure to degrade a key component, the Smaug RNA-binding protein, disrupts an orderly maternal-to-zygotic transition.