Role of the Translin/Trax complex in RNA processing.

摘要

Translin and Trax are evolutionarily conserved proteins that form an RNA binding complex whose) function is still under investigation. Since immunohistochemical studies indicate that Translin has a somatodendritic staining pattern in neurons, it has been suggested that this complex may play a role in trafficking and/or translation of dendritic transcripts. More recent studies have implicated this complex in regulating microRNA processing in Drosophila by facilitating loading of the RNA-induced silencing complex (RISC). Initial collaborative studies with Dr. Tongiorgi's laboratory indicated that knock-down of Translin impaired KCl-induced dendritic trafficking of Brain-derived neurotrophic factor (BDNF) mRNA in cultured neurons. Therefore, I tested whether dendritic BDNF mRNA trafficking is impaired in the Translin knock-out mice in vivo. These studies indicate that the basal level of BDNF mRNA in dendrites is decreased in Translin knock-out mice and that the ability of pilocarpine-induced seizure activity to trigger dendritic targeting of BDNF mRNA is preserved in these mice. Based on these in vivo findings, we infer that the dependence of BDNF mRNA localization on Translin is not absolute but stimulus-dependent. This interpretation is consistent with studies from the Tongiorgi lab showing that knock-down of Translin blocks dendritic trafficking of BDNF mRNA induced by KCl but not by BDNF protein. We also present the results of ongoing preliminary studies aimed at assessing whether the Translin/Trax complex plays a role in microRNA processing in mammalian cells. Taken together, these findings indicate that future studies are warranted to assess whether Translin regulates BDNF mRNA expression and localization via its influence on microRNA processing.