Using a biochemical approach to a longstanding problem in Drosophila genetics, Wilhelm et al. (page 1197) have identified a novel protein that links translational repression to mRNA localization and also uncovered a surprisingly specific localization pattern for a ubiquitous translation factor.
Polarized cells often rely on mRNA localization to restrict protein distribution. During fly oocyte development, for example, oskar mRNA moves from the posterior end of the oocyte to an anterior position, then back to the posterior end before being translated. As Oskar expression determines posterior patterning and germline establishment, the mRNA must be repressed until it reaches its final position. Something must coordinate the localization and translational repression of the message, but genetic studies have only found mutants that affected localization or repression, not both.
Wilhelm et al. now identify the product of the Cup gene as the missing link. Cup is part of a multiprotein complex that copurifies with oskar mRNA. Interfering with Cup disrupts both the localization and translational repression of oskar. Surprisingly, the ubiquitous translation factor eIF4E, which is generally assumed to be homogeneously distributed in cells, specifically binds to Cup and substantially localizes to the posterior end of fly oocytes.
The authors propose a model in which Cup binds to oskar mRNA as a repressor and also recruits the transport components of the protein complex. Once the mRNA reaches its destination, a posterior signal could then disrupt the Cup–eIF4E interaction and permit translation. Since the need to coordinate repression with mRNA localization is common to many polarized cells, recruiting transport components could be a feature of many translational repressors. The authors are now examining Drosophila mutants with phenotypes similar to Cup in an effort to identify additional mRNA regulators.
