RNA localization

The initial steps in cell fate specification, embryonic patterning, and cellular differentiation involve the establishment of intracellular asymmetry. These asymmetries are established by the selective localization of vesicles, organelles, or macromolecules. Over the past decade it has become evident that localization of RNA molecules is a key method for producing cellular asymmetry in organisms as diverse as yeast and humans. This issue of the journal contains four reviews that address the mechanisms and functions of RNA localization in different animal species and in distinct cell types. It has been clearly demonstrated in Drosophila oocytes that mRNA localization usually functions to spatially restrict the production of the encoded protein (1, 2). Several examples have also been described in somatic cells (reviewed in Bassell et al.). RNA localization thus serves two complementary functions: first, it results in a high local concentration of the protein; second, it prevents high levels of the protein from being present elsewhere. A further function of RNA localization has been uncovered in oocytes and embryos. Here, diffusion of the protein from its RNA source leads to the establishment of a protein gradient, which provides spatial information to the cells that come to reside in different parts of the gradient (best exemplified by bicoid and nanos RNA localization in Drosophila; ref 1). In principle, such a gradient could also be used in any large cell to provide polarized intracellular information. RNA localization also has been implicated in the binary decisions involved in the specification of cell fates and the establishment of embryonic germ layers. This is accomplished through asymmetric segregation of localized transcripts into only one of the two cells produced by mitosis, causing the encoded protein to be restricted to only that cell. Examples include the role of prospero in differentiating neuroblasts in Drosophila (1), ASH1 in the determination of mating type in budding yeast (3, 4), and VegT in the establishment of the embryonic germ layers in Xenopus (2). The importance of mRNA localization in restricting the spatial distribution of the encoded protein is further highlighted by the discovery of a link between RNA localization and translation. In Drosophila, oskar and nanos transcripts are localized to and translated at the posterior pole of the oocyte (1). These transcripts are translationally repressed either during their transport to the posterior (oskar) or if they fail to be localized (nanos). Translational control of localized RNAs may be intimately linked, on one hand, to translation factors that are integral components of localization particles, and on the other hand to association with the cytoskeleton (3, 4). Apart from mRNAs, there are now several examples of localized non-protein-coding RNAs in Xenopus (e.g., Xlsirts; ref 2), Drosophila (e.g., Pgc; ref 1), and mammalian somatic cells (e.g., BC1; refs 3, 4). These may serve as structural components of particular organelles such as the germinal granules, function in RNA transport, or be involved in transcript anchoring to the cytoskeleton. Identification1 of the components of the RNA sorting, transport, and localization apparatus is proceeding at a rapid pace and is leading to insights not only into localization mechanisms, but also into how these mechanisms may have evolved. For example, several individual cis-acting localization elements have been found to contribute to compound cisacting domains, usually located within the 39 UTR of the cognate mRNAs (1–4). Each element encodes a subset of the information necessary for RNA localization. Trans-acting factors that interact with these elements are now being identified. Evolutionary conservation of localization mechanisms is highlighted by the fact that the mammalian zip code binding protein involved in the localization of b-actin transcripts in fibroblasts is homologous with the Vera protein involved in the localization of Vg1 transcripts in Xenopus oocytes (2, 4). In Drosophila it has been shown that cis-acting elements involved in transla-