April n&v final

NATURE CELL BIOLOGY VOLUME 6 | NUMBER 4 | APRIL 2004 285 Messenger RNA localization and the translational repression of unlocalized mRNA have a pivotal role in patterning the future embryo within the Drosophila oocyte (Fig. 1). Three key transcripts have been extensively studied: bicoid (bcd), gurken (grk) and oskar (osk). bcd mRNA is localized to the anterior of the oocyte and encodes a morphogen that establishes the anterior–posterior axis in the embryo1, whereas grk mRNA is localized near the oocyte nucleus and restricts the distribution of a transforming growth factor α (TGFα) signal that establishes both the anterior–posterior and dorso-ventral axes in the oocyte. Finally, osk mRNA localization in the posterior, together with the translational repression of unlocalized osk mRNA, targets Osk protein to the posterior. At this site, Osk protein is sufficient to trigger the recruitment of the other mRNAs and proteins that are required to specify the germ cells and abdomen of the future embryo and fly2. All three transcripts require specific microtubuleassociated molecular motors for their localization3–5, and a key remaining question is how RNA signals are interpreted by trans-acting factors and sorted to their correct destinations by molecular motors. Reporting in Nature6, Palacios et al. now identify the putative RNA helicase and translational initiation factor eIF4AIII as a new factor required for osk mRNA localization. They suggest that specificity may be conferred by the interactions of multiple factors at different stages of an mRNA’s transit. A priori, it seemed reasonable to assume that the sorting of transcripts to distinct destinations would be defined by a simple RNA signal to which a single trans-acting factor binds, providing a specific link to an appropriate motor. Indeed, this is the case for yeast ASH1 mRNA: She2p and She3p link ASH1 RNA to the myosin motor required for its localization7. However, it is not that simple in Drosophila. Single-specificity determinants have not been found for bcd, osk or grk mRNA, and specific destinations are most probably defined by many trans-acting factors that vary considerably in their composition during different stages of the complex journey of an RNA — from its site of transcription to its final cytoplasmic destination. For example, the bcd 3′-untranslated region (UTR) localization signal is decorated by several factors that might all be involved in its localization8. Similarly, osk mRNA always colocalizes with Staufen (a double-stranded RNA-binding protein essential for its localization), but Staufen alone cannot determine its transcript destination as it also binds to bcd. Furthermore, osk mRNA localization requires, among other factors, a nuclear exon junction complex (EJC)9 containing Mago nashi (Mago) and Y14 (Mago-Y14), which has been shown in human cells to mark the location on a spliced transcript where introns have been removed. Palacios and colleagues6 add an exciting new layer of complexity to how cytoplasmic transcript destination is selected, at least in the case of osk mRNA. They show that Barentsz (Btz) — a trans-acting factor required for osk mRNA localization — interacts with Drosophila eIF4AIII both genetically and physically. EIF4AIII is a DEAD-box helicase that is homologous to the translation initiation factor eIF4AI, although its role in translation remains unclear10. So is eIF4AIII required, similarly to Btz, for osk mRNA localization, A helicase that gets Oskar’s message across