The spatial organization of proteins within cells is critical to their proper function. This is especially true in polarized cells and those with elongated structures like neurons. This spatial arrangement can be achieved by transporting fully translated proteins to their required destination. Alternatively, it can be done by transporting the instructions for making the protein, that is, an mRNA, to the desired location followed by on site protein production. The latter method has several advantages, including the allowance of rapid and robust translational responses to received stimuli. This RNA localization strategy is used widely in neurons. Approximately one thousand RNA transcripts are localized to the projections of neuronal cells (neurites). Their localization is controlled through the interaction cis RNA sequences in the transcripts (so called zipcodes for their ability to induce spatial sorting) and protein factors that bind these sequences and facilitate their movement. Of the approximately one thousand localized transcripts in neurons, the zipcodes that control their localization are known for only 10-20, representing a large gap in our understanding of this process. Mutations in the RNA-binding proteins that mediate RNA transport are associated with neurological disease, emphasizing the importance of RNA localization in the physiology of neuronal cells.
Active areas of research include (1) the mechanisms by which RNA-binding proteins involved in localization recognize and bind their mRNA targets, (2) high-throughput screening to identify RNA sequences with the ability to drive localization to neurites, and (3) the dynamic changes in localized transcriptomes in response to stimuli.
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