Translational control ofgurkenmRNA inDrosophiladevelopment

Abstract

Localized mRNA translation is a widespread mechanism for targeting protein synthesis, important for cell fate, motility and pathogenesis. In Drosophila, the spatiotemporal control of gurken/TGF-a mRNA translation is required for establishing the embryonic body axes. A number of recent studies have highlighted key aspects of the mechanism of gurken mRNA translational control at the dorsoanterior corner of the mid-stage oocyte. Orb/CPEB and Wispy/GLD-2 are required for polyadenylation of gurken mRNA, but unlocalized gurken mRNA in the oocyte is not fully polyadenylated.1 At the dorsoanterior corner, Orb and gurken mRNA have been shown to be enriched at the edge of Processing bodies, where translation occurs.2 Over-expression of Orb in the adjacent nurse cells, where gurken mRNA is transcribed, is sufficient to cause mis-expression of Gurken protein.3 In orb mutant egg chambers, reducing the activity of CK2, a Serine/Threonine protein kinase, enhances the ventralized phenotype, consistent with perturbation of gurken translation. 4 Here we show that sites phosphorylated by CK2 overlap with active Orb and with Gurken protein expression. Together with our new findings we consolidate the literature into a working model for gurken mRNA translational control and review the role of kinases, cell cycle factors and polyadenylation machinery highlighting a multitude of conserved factors and mechanisms in the Drosophila egg chamber.

Auto-regulatory feedback by RNA-binding proteins

“…The Orb protein shares homology with the vertebrate cytoplasmic polyadenylation element-binding proteins (CPEBs) involved in the regulation of protein synthesis via control of poly(A)-tail length (Mendez and Richter, 2001). It has been proposed that Orb-mediated translational activation of the oskar and gurken mRNAs, as well as its auto-regulatory activity, are mediated by cytoplasmic polyadenylation that enhances RNA stability and translation (Chang et al, 1999; Tan et al, 2001; Derrick and Weil, 2017).…”

Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

“…26 ] in homozygosis. In wild-type flies, association of Orb with RNPs selectively occurs in the oocyte 27 , 28 . By contrast, in Hecw mutant animals altered Orb puncta fully colocalise with Me31B in the cytoplasm of nurse cells of previtellogenic and early vitellogenic egg chambers (Fig.…”

The ubiquitin ligase Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

“…22 ). In wild-type flies association of Orb with RNPs selectively occurs in the oocyte 23,24 . By contrast, in Hecw mutant animals altered Orb puncta fully colocalise with Me31B in the cytoplasm of nurse cells of previtellogenic and early vitellogenic egg chambers ( Fig.…”

“…The lower exchange rate between RNPs and the cytoplasm is specific of Hecw mutant granules and possibly reflects an altered internal rearrangement and activity of the proteins present inside these membrane-less particles. Indeed, the Orb protein that is usually absent in the nurse cells granules 23,24 , is clearly present in the larger Hecw-depleted…”