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Abstract Ataxin‐2, a conserved RNA‐binding protein, is implicated in the late‐onset neurodegenerative disease Spinocerebellar ataxia type‐2 (SCA2). SCA2 is characterized by shrunken dendritic arbors and torpedo‐like axons within the Purkinje neurons of the cerebellum. Torpedo‐like axons have been described to contain displaced endoplasmic reticulum (ER) in the periphery of the cell; however, the role of Ataxin‐2 in mediating ER function in SCA2 is unclear. We utilized theCaenorhabditis elegansandDrosophilahomologs of Ataxin‐2 (ATX‐2 and DAtx2, respectively) to determine the role of Ataxin‐2 in ER function and dynamics in embryos and neurons. Loss of ATX‐2 and DAtx2 resulted in collapse of the ER in dividing embryonic cells and germline, and ultrastructure analysis revealed unique spherical stacks of ER in mature oocytes and fragmented and truncated ER tubules in the embryo. ATX‐2 and DAtx2 reside in puncta adjacent to the ER in bothC. elegansandDrosophilaembryos. Lastly, depletion of DAtx2 in culturedDrosophilaneurons recapitulated the shrunken dendritic arbor phenotype of SCA2. ER morphology and dynamics were severely disrupted in these neurons. Taken together, we provide evidence that Ataxin‐2 plays an evolutionary conserved role in ER dynamics and morphology inC. elegansandDrosophilaembryos during development and in fly neurons, suggesting a possible SCA2 disease mechanism. 

RNA regulation plays a critical role in mitosis, yet the mechanisms remain unclear. Our lab recently identified that the conserved RNA-Binding Protein (RBP), ATX-2, regulates cytokinesis by regulating the targeting of ZEN-4 to the spindle midzone through a conserved translation regulator, PAR-5/14-3-3sigma (Gnazzo et al., 2016). While co-depletion of ATX-2 and PAR-5 restored ZEN-4 targeting to the spindle midzone, it did not rescue cell division. To identify factors that may work in concert with ATX-2 to regulate cell division, we conducted a two-part, candidate RNAi suppressor and visual screen to identify factors that are important for cell division and also mediate the targeting of ATX-2 to the centrosomes and the spindle midzone. Using this approach, we identified ten genes that suppress the embryonic lethality defect observed in atx-2 mutant embryos. These ten genes, including act-2, cgh-1, cki-1, hum-6, par-2, rnp-4, vab-3, vhl-1, vps-24, and wve-1, all have some role regulating RNA or the cell cycle. Five of these genes (cgh-1, cki-1, vab-3, vhl-1, vps-24) fail to target ATX-2 to the centrosomes and midzone when depleted. The strongest suppressor of the atx-2 phenotype is the DEAD-box RNA helicase CGH-1/DDX6, which has been implicated in cell division, RNA processing and translation, and neuronal function. Loss of CGH-1 rescued the cytokinesis defect and also restored ZEN-4 localization to the spindle midzone. ATX-2 and CGH-1 are mutually required for their localization to centrosomes and the spindle midzone. Our findings provide the first functional evidence that CGH-1/DDX6 regulates ATX-2 function during mitosis to target ZEN-4 to the spindle midzone via PAR-5/14-3-3sigma. We suggest that RNA machinery is necessary for the completion of cytokinesis.