bicoid RNA localization requires specific binding of an endosomal sorting complex

    loading  Checking for direct PDF access through Ovid

Abstract

bicoidmessenger RNA localizes to the anterior of theDrosophilaegg, where it is translated to form a morphogen gradient of Bicoid protein that patterns the head and thorax of the embryo. Althoughbicoidwas the first localized cytoplasmic determinant to be identified1-4, little is known about how the mRNA is coupled to the microtubule-dependent transport pathway that targets it to the anterior, and it has been proposed that the mRNA is recognized by a complex of many redundant proteins, each of which binds to the localization element in the 3′ untranslated region (UTR) with little or no specificity5. Indeed, the only known RNA-binding protein that co-localizes withbicoidmRNA is Staufen, which binds non-specifically to double-stranded RNAin vitro6,7. Here we show that mutants in all subunits of the ESCRT-II complex (VPS22, VPS25 and VPS36) abolish the final Staufen-dependent step inbicoidmRNA localization. ESCRT-II is a highly conserved component of the pathway that sorts ubiquitinated endosomal proteins into internal vesicles8,9, and functions as a tumour-suppressor by removing activated receptors from the cytoplasm10,11. However, the role of ESCRT-II inbicoidlocalization seems to be independent of endosomal sorting, because mutations in ESCRT-I and III components do not affect the targeting ofbicoidmRNA. Instead, VPS36 functions by binding directly and specifically to stem-loop V of thebicoid3′ UTR through its amino-terminal GLUE domain12, making it the first example of a sequence-specific RNA-binding protein that recognizes thebicoidlocalization signal. Furthermore, VPS36 localizes to the anterior of the oocyte in abicoid-mRNA-dependent manner, and is required for the subsequent recruitment of Staufen to thebicoidcomplex. This function of ESCRT-II as an RNA-binding complex is conserved in vertebrates and may clarify some of its roles that are independent of endosomal sorting.

Related Topics

    loading  Loading Related Articles