Pumilio and Brain tumor regulate the expression of Smaug during the Drosophila maternal-to-zygotic transition

Authors

Smibert, C. A., Marsolais, A. J., Kekis, M., Smith, H. W., Wang, Z., Weerasooriya, C., Hughes, T. R., Lipshitz, H. D.

Abstract

During the Drosophila maternal-to-zygotic transition, maternally deposited RNAs are cleared in a temporally controlled manner. The RNA-binding protein Smaug is a major regulator of maternal mRNA decay and its expression at both the RNA and protein level is limited to a narrow temporal window during the MZT. Here we show that Pumilio RNA-binding protein promotes degradation of smaug mRNA at the end of the MZT through Pumilio-binding cis-elements in the smaug 3 untranslated region, and that disruption of this regulation leads to ectopic Smaug protein expression beyond its normal developmental window. We further find that another RNA-binding protein, Brain tumor, also contributes to repression of ectopic Smaug expression. Transcriptome-wide analyses of embryos lacking Pumilio reveal that it directly regulates hundreds of maternal mRNAs after zygotic genome activation, with many of these Pumilio targets also regulated by Brain tumor. The ectopic Smaug protein that results from loss of either Pumilio or Brain tumor causes widespread downregulation of mRNAs that contain Smaug binding sites. Together, these findings define a post-transcriptional regulatory pathway in which Pumilio and Brain tumor ensure orderly progression of the Drosophila maternal-to-zygotic by clearing smaug mRNA and preventing ectopic Smaug activity.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 22 Aug 2026.

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