P111. RNG105 deficiency impairs the dendritic transport of mRNA and leads to the degeneration of neuronal networks

Abstract

mRNA transport and subsequent local translation are key mechanisms for several cellular processes during development. In neurons, local translation in dendrites plays important roles in use-dependent synaptic modification and in higher-order brain functions. RNA granules that consist of clusters of ribosomes and mRNAs play central roles in the mRNA transport and local translational control in neuronal dendrites. We identified RNG105 (RNA granule protein 105) as a novel RNA-binding protein that localizes to RNA granules in neurons. We further identified RNG105-associated mRNAs, which included mRNAs encoding Na+/K+ ATPase (NKA) subunit isoforms, i.e., α3, FXYD1, FXYD6, and FXYD7. We generated RNG105-knockout mice and found that the mice died soon after birth because of respiratory failure, suggesting that their brainstem function was impaired. In Rng105–/– neurons, dendritic localization of the NKA mRNAs was reduced, which was accompanied by the loss of function of NKA in dendrites without affecting the NKA function in the soma. Furthermore, Knockout of RNG105 impaired the formation of synapses and neuronal networks, which was mimicked by inhibition and knockdown of NKA in neurons. We propose that RNG105 participates in the dendritic transport of the mRNAs to regulate the development and maintenance of functional networks.