Directional Transport of Transcripts by Cytoplasmic Motor-Protein Complexes

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In eukaryotes, directional transport of cytoplasmic mRNA and subsequent localized expression of transcripts is a powerful mechanism to achieve cellular asymmetry, which is a prerequisite for cell differentiation and the development of multi-cellular organisms. In addition, directional mRNA-transport is utilized in neurons for pre- and post-synaptic protein expression to generate neuronal plasticity. Thus far, the only comprehensively characterized example for directional mRNA transport is the translocation of ASH1 mRNA in the budding yeast Saccharomyces cerevisiae.Besides ASH1 mRNA, the transport complex consists of the mRNA-binding protein She2p, which binds to four elements within the ASH1 mRNA, the adapter protein She3p, and the myosin type V motor protein Myo4p (Figure 1A). We recently showed by X-ray crystallography that She2p is a novel type of RNA-binding protein (Niessing et al., 2004). By using a combination of X-ray crystallography, biophysical, biochemical, and in vivo techniques, we now aim to characterize the molecular basis for motor-protein-dependent cargo transport at atomic resolution. With such a multidisciplinary approach, we attempt to understand how the core factors of the ASH1 mRNP interact to (i) detect their cargo mRNA, (ii) assemble into a cargo-specific, functional complex in response to ASH1 mRNA recognition by She2p, and (iii) translocate ASH1 mRNA through the cytoplasm.