Role of Purα in Targeting mRNA to Sites of Translation in Hippocampal Neuronal Dendrites

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Abstract

Using genetic inactivation in the mouse, PURA, encoding Purα, is demonstrated to be essential for developmentally-timed dendrite formation in the cerebellum and hippocampus. Comparison of RNA species bound by Purα prompts the hypothesis that Purα functions with non-coding RNA in transport of certain mRNA molecules to sites of translation in dendrites. Purα binds to human BC200 RNA, implicated in dendritic targeting, and this has homologies to 7SL RNA, implicated in compartmentalized translation. Results using hippocampal rat neurons in situ show that Purα binds to BC1 RNA, implicated in dendritic targeting as a mouse counterpart of BC200, and to mRNA molecules translated in dendrites; Purα is specifically located in dendrites, where it is colocalized with Map2, but not in axons, where it fails to colocalize with Ankyrin G. Purα and Staufen are colocalized at dendritic sites of mRNA translation. Microtubule disruptors inhibit Purα dendritic targeting and allow its mislocalization to axons. Using mouse brain, double-RNA immunoprecipitation places Purα together with Staufen or FMRP on BC1 RNA and specific mRNA species in vivo. These results help define a mechanism by which Purα targets specific mRNA molecules to sites of dendritic translation.

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