Assembly of mRNA-protein complexes for directional mRNA transport in eukaryotes--an overview

Abstract

At all steps from transcription to translation, RNA-binding proteins play important roles in determining mRNA function. Initially it was believed that for the vast majority of transcripts the role of RNA-binding proteins is limited to general functions such as splicing and translation. However, work from recent years showed that members of this class of proteins also recognize several mRNAs via cis-acting elements for their incorporation into large motor-containing particles. These particles are transported to distant subcellular sites, where they become subsequently translated. This process, called mRNA localization, occurs along microtubules or actin filaments, and involves kinesins, dyneins, as well as myosins. Although mRNA localization has been detected in a large number of organisms from fungi to humans, the underlying molecular machineries are not well understood. In this review we will outline general principles of mRNA localization and highlight three examples, for which a comparably large body of information is available. The first example is She2p/She3p-dependent localization of ASH1 mRNA in budding yeast. It is particularly well suited to highlight the interdependence between different steps of mRNA localization. The second example is Staufen-dependent localization of oskar mRNA in the Drosophila embryo, for which the importance of nuclear events for cytoplasmic localization and translational control has been clearly demonstrated. The third example summarizes Egalitarian/Bicaudal D-dependent mRNA transport events in the oocyte and embryo of Drosophila. We will highlight general themes and differences, point to similarities in other model systems, and raise open questions that might be answered in the coming years.

Fig. (1)

Three mechanisms for asymmetric subcellular mRNA distribution. Left: Diffusion and cytoplasmic streaming bring mRNAs to particular sites of a cell and allow for their transcript-specific subcellular anchoring. Middle: Asymmetric mRNA degradation results in local depletion of transcripts and cellular asymmetry of a particular mRNA. RNase activity is depicted as scissors. Right: Directional mRNA transport by motor-protein containing particles along microtubules or actin filaments is the most efficient way to ensure strictly localized translation of particular transcripts. Combinations of these three mechanisms are possible.

Fig. (2)

Motor-dependent mRNA localization. A: General model for mRNA localization. On top is an outline of the main stages of this process. Nuclear priming and cell cortex association/anchoring are not necessarily present in all mRNA localization events. B: ASH1 mRNA localization during mitosis of the budding yeast Saccharomyces cerevisisae. This active transport event is mediated by a type V myosin motor towards the plus-ends of actin filaments. To date, it constitutes the most comprehensively understood mRNA localization event.